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2000
Volume 25, Issue 2
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Inflammatory bowel disease (IBD), a chronic inflammatory condition of the human intestine, comprises Crohn’s disease (CD) and ulcerative colitis (UC). IBD causes severe gastrointestinal symptoms and increases the risk of developing colorectal carcinoma. Although the etiology of IBD remains ambiguous, complex interactions between genetic predisposition, microbiota, epithelial barrier, and immune factors have been implicated. The disruption of intestinal homeostasis is a cardinal characteristic of IBD. Patients with IBD exhibit intestinal microbiota dysbiosis, impaired epithelial tight junctions, and immune dysregulation; however, the relationship between them is not completely understood. As the largest body surface is exposed to the external environment, the gastrointestinal tract epithelium is continuously subjected to environmental and endogenous stressors that can disrupt cellular homeostasis and survival. Heat shock proteins (HSPs) are endogenous factors that play crucial roles in various physiological processes, such as maintaining intestinal homeostasis and influencing IBD progression. Specifically, HSPs share an intricate association with microbes, intestinal epithelium, and the immune system. In this review, we aim to elucidate the impact of HSPs on IBD development by examining their involvement in the interactions between the intestinal microbiota, epithelial barrier, and immune system. The recent clinical and animal models and cellular research delineating the relationship between HSPs and IBD are summarized. Additionally, new perspectives on IBD treatment approaches have been proposed.

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References

  1. SrivastavaP. Roles of heat-shock proteins in innate and adaptive immunity.Nat. Rev. Immunol.20022318519410.1038/nri749 11913069
    [Google Scholar]
  2. GongM. ZhangF. MiaoY. NiuJ. Advances of heat shock family in ulcerative colitis.Front. Pharmacol.20221386993010.3389/fphar.2022.869930 35645809
    [Google Scholar]
  3. KampingaH.H. HagemanJ. VosM.J. Guidelines for the nomenclature of the human heat shock proteins.Cell Stress Chaperones200914110511110.1007/s12192‑008‑0068‑7 18663603
    [Google Scholar]
  4. LiuH. DicksvedJ. LundhT. LindbergJ. Heat shock proteins: Intestinal gatekeepers that are influenced by dietary components and the gut microbiota.Pathogens20143118721010.3390/pathogens3010187 25437614
    [Google Scholar]
  5. NickelW. Pathways of unconventional protein secretion.Curr. Opin. Biotechnol.201021562162610.1016/j.copbio.2010.06.004 20637599
    [Google Scholar]
  6. NickelW. SeedorfM. Unconventional mechanisms of protein transport to the cell surface of eukaryotic cells.Annu. Rev. Cell Dev. Biol.200824128730810.1146/annurev.cellbio.24.110707.175320 18590485
    [Google Scholar]
  7. ZiningaT. RamatsuiL. ShonhaiA. Heat shock proteins as immunomodulants.Molecules20182311284610.3390/molecules23112846 30388847
    [Google Scholar]
  8. FerrariniM. HeltaiS. ZocchiM.R. RugarliC. Unusual expression and localization of heat‐shock proteins in human tumor cells.Int. J. Cancer199251461361910.1002/ijc.2910510418 1601523
    [Google Scholar]
  9. CalderwoodS.K. GongJ. MurshidA. Extracellular HSPs: The complicated roles of extracellular HSPs in immunity.Front. Immunol.2016715910.3389/fimmu.2016.00159 27199984
    [Google Scholar]
  10. De MaioA. VazquezD. Extracellular heat shock proteins: A new location, a new function.Shock201340423924610.1097/SHK.0b013e3182a185ab 23807250
    [Google Scholar]
  11. NadeemM.S. KumarV. Al-AbbasiF.A. KamalM.A. AnwarF. Risk of colorectal cancer in inflammatory bowel diseases.Semin. Cancer Biol.202064516010.1016/j.semcancer.2019.05.001 31112753
    [Google Scholar]
  12. JessT. GamborgM. MatzenP. MunkholmP. SørensenT.I.A. Increased risk of intestinal cancer in Crohn’s disease: A meta-analysis of population-based cohort studies.Am. J. Gastroenterol.2005100122724272910.1111/j.1572‑0241.2005.00287.x 16393226
    [Google Scholar]
  13. HoterA. NaimH.Y. The functions and therapeutic potential of heat shock proteins in inflammatory bowel disease—An update.Int. J. Mol. Sci.20192021533110.3390/ijms20215331 31717769
    [Google Scholar]
  14. UhligH.H. PowrieF. Translating immunology into therapeutic concepts for inflammatory bowel disease.Annu. Rev. Immunol.201836175578110.1146/annurev‑immunol‑042617‑053055 29677472
    [Google Scholar]
  15. JostinsL. RipkeS. WeersmaR.K. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease.Nature2012491742211912410.1038/nature11582 23128233
    [Google Scholar]
  16. TorresJ. MehandruS. ColombelJ.F. BirouletP.L. Crohn’s disease.Lancet2017389100801741175510.1016/S0140‑6736(16)31711‑1 27914655
    [Google Scholar]
  17. UngaroR. MehandruS. AllenP.B. BirouletP.L. ColombelJ.F. Ulcerative colitis.Lancet2017389100801756177010.1016/S0140‑6736(16)32126‑2 27914657
    [Google Scholar]
  18. PeloquinJ.M. GoelG. VillablancaE.J. XavierR.J. Mechanisms of pediatric inflammatory bowel disease.Annu. Rev. Immunol.2016341316410.1146/annurev‑immunol‑032414‑112151 27168239
    [Google Scholar]
  19. NgS.C. ShiH.Y. HamidiN. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies.Lancet2017390101142769277810.1016/S0140‑6736(17)32448‑0 29050646
    [Google Scholar]
  20. KaplanG.G. The global burden of IBD: from 2015 to 2025.Nat. Rev. Gastroenterol. Hepatol.2015121272072710.1038/nrgastro.2015.150 26323879
    [Google Scholar]
  21. FrankD.N. St AmandA.L. FeldmanR.A. BoedekerE.C. HarpazN. PaceN.R. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases.Proc. Natl. Acad. Sci.200710434137801378510.1073/pnas.0706625104 17699621
    [Google Scholar]
  22. CarusoR. LoB.C. NúñezG. Host–microbiota interactions in inflammatory bowel disease.Nat. Rev. Immunol.202020741142610.1038/s41577‑019‑0268‑7 32005980
    [Google Scholar]
  23. HondaK. LittmanD.R. The microbiome in infectious disease and inflammation.Annu. Rev. Immunol.201230175979510.1146/annurev‑immunol‑020711‑074937 22224764
    [Google Scholar]
  24. ManichanhC. GoisR.L. BonnaudE. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach.Gut200655220521110.1136/gut.2005.073817 16188921
    [Google Scholar]
  25. PetersonD.A. FrankD.N. PaceN.R. GordonJ.I. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases.Cell Host Microbe20083641742710.1016/j.chom.2008.05.001 18541218
    [Google Scholar]
  26. CrunkhornS. Yeast probiotics treat IBD.Nat. Rev. Drug Discov.202120858810.1038/d41573‑021‑00116‑5 34234307
    [Google Scholar]
  27. ZhouJ. LiM. ChenQ. Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery.Nat. Commun.2022131343210.1038/s41467‑022‑31171‑0 35701435
    [Google Scholar]
  28. HuoX. LiD. WuF. Cultivated human intestinal fungus Candida metapsilosis M2006B attenuates colitis by secreting acyclic sesquiterpenoids as FXR agonists.Gut202271112205221710.1136/gutjnl‑2021‑325413 35173042
    [Google Scholar]
  29. LiJ. SunM. LiuL. Nanoprobiotics for remolding the pro-inflammatory microenvironment and microbiome in the treatment of colitis.Nano Lett.202323188593860110.1021/acs.nanolett.3c02408 37625135
    [Google Scholar]
  30. XieA. JiH. LiuZ. Modified prebiotic-based “Shield” armed probiotics with enhanced resistance of gastrointestinal stresses and prolonged intestinal retention for synergistic alleviation of colitis.ACS Nano20231715147751479110.1021/acsnano.3c02914 37477584
    [Google Scholar]
  31. GillilandA. ChanJ.J. De WolfeT.J. YangH. VallanceB.A. Pathobionts in inflammatory bowel disease: Origins, underlying mechanisms, and implications for clinical care.Gastroenterology20241661445810.1053/j.gastro.2023.09.019 37734419
    [Google Scholar]
  32. ChenQ. FanY. ZhangB. Capsulized fecal microbiota transplantation induces remission in patients with ulcerative colitis by gut microbial colonization and metabolite regulation.Microbiol. Spectr.2023113e04152e2210.1128/spectrum.04152‑22 37093057
    [Google Scholar]
  33. PorcariS. SeverinoA. RondinellaD. Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis.J. Autoimmun.202314110303310.1016/j.jaut.2023.103033 37085337
    [Google Scholar]
  34. UlluwishewaD. AndersonR.C. McNabbW.C. MoughanP.J. WellsJ.M. RoyN.C. Regulation of tight junction permeability by intestinal bacteria and dietary components.J. Nutr.2011141576977610.3945/jn.110.135657 21430248
    [Google Scholar]
  35. MadsenK. CornishA. SoperP. Probiotic bacteria enhance murine and human intestinal epithelial barrier function.Gastroenterology2001121358059110.1053/gast.2001.27224 11522742
    [Google Scholar]
  36. GuptaP. AndrewH. KirschnerB.S. GuandaliniS. Is lactobacillus GG helpful in children with Crohn’s disease? Results of a preliminary, open-label study.J. Pediatr. Gastroenterol. Nutr.200031445345710.1097/00005176‑200010000‑00024 11045848
    [Google Scholar]
  37. HuS. WangY. LichtensteinL. Regional differences in colonic mucosa-associated microbiota determine the physiological expression of host heat shock proteins.Am. J. Physiol. Gastrointest. Liver Physiol.20102996G1266G127510.1152/ajpgi.00357.2010 20864653
    [Google Scholar]
  38. BeckS.C. PaidasC.N. MooneyM.L. DeitchE.A. De MaioA. Presence of the stress-inducible form of hsp-70 (hsp-72) in normal rat colon.Shock199536398402 7656062
    [Google Scholar]
  39. KojimaK. MuschM.W. RenH. Enteric flora and lymphocyte-derived cytokines determine expression of heat shock proteins in mouse colonic epithelial cells.Gastroenterology200312451395140710.1016/S0016‑5085(03)00215‑4 12730879
    [Google Scholar]
  40. BowcuttR. FormanR. GlymenakiM. CardingS.R. ElseK.J. CruickshankS.M. Heterogeneity across the murine small and large intestine.World J. Gastroenterol.20142041152161523210.3748/wjg.v20.i41.15216 25386070
    [Google Scholar]
  41. TaoY. DrabikK.A. WaypaT.S. Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells.Am. J. Physiol. Cell Physiol.20062904C1018C103010.1152/ajpcell.00131.2005 16306130
    [Google Scholar]
  42. NemethE. FajdigaS. MalagoJ. KoninkxJ. TootenP. van DijkJ. Inhibition of Salmonella-induced IL-8 synthesis and expression of Hsp70 in enterocyte-like Caco-2 cells after exposure to non-starter lactobacilli.Int. J. Food Microbiol.2006112326627410.1016/j.ijfoodmicro.2006.09.002 17045688
    [Google Scholar]
  43. LiuH.Y. GuF. ZhuC. Epithelial heat shock proteins mediate the protective effects of Limosilactobacillus reuteri in dextran sulfate sodium-induced colitis.Front. Immunol.20221386598210.3389/fimmu.2022.865982 35320932
    [Google Scholar]
  44. PetrofE.O. KojimaK. RopeleskiM.J. Probiotics inhibit nuclear factor-κB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition.Gastroenterology200412751474148710.1053/j.gastro.2004.09.001 15521016
    [Google Scholar]
  45. MalagoJ.J. KoninkxJ.F.J.G. OvelgönneH.H. van AstenF.J.A.M. SwennenhuisJ.F. van DijkJ.E. Expression levels of heat shock proteins in enterocyte-like Caco-2 cells after exposure to Salmonella enteritidis.Cell Stress Chaperones20038219420310.1379/1466‑1268(2003)008<0194:ELOHSP>2.0.CO;2 14627205
    [Google Scholar]
  46. NahoumR.S. PaglinoJ. VarzanehE.F. EdbergS. MedzhitovR. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.Cell2004118222924110.1016/j.cell.2004.07.002 15260992
    [Google Scholar]
  47. SegawaS. FujiyaM. KonishiH. Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway.PLoS One201168e2327810.1371/journal.pone.0023278 21858054
    [Google Scholar]
  48. UenoN. FujiyaM. SegawaS. Heat-killed body of lactobacillus brevis SBC8803 ameliorates intestinal injury in a murine model of colitis by enhancing the intestinal barrier function.Inflamm. Bowel Dis.201117112235225010.1002/ibd.21597 21987297
    [Google Scholar]
  49. OkamotoK. FujiyaM. NataT. Competence and sporulation factor derived from Bacillus subtilis improves epithelial cell injury in intestinal inflammation via immunomodulation and cytoprotection.Int. J. Colorectal Dis.20122781039104610.1007/s00384‑012‑1416‑8 22297864
    [Google Scholar]
  50. FujiyaM. MuschM.W. NakagawaY. The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter.Cell Host Microbe20071429930810.1016/j.chom.2007.05.004 18005709
    [Google Scholar]
  51. KojimaK. MuschM.W. RopeleskiM.J. BooneD.L. MaA. ChangE.B. Escherichia coli LPS induces heat shock protein 25 in intestinal epithelial cells through MAP kinase activation.Am. J. Physiol. Gastrointest. Liver Physiol.20042864G645G65210.1152/ajpgi.00080.2003 14630641
    [Google Scholar]
  52. RenH. MuschM.W. KojimaK. BooneD. MaA. ChangE.B. Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells.Gastroenterology2001121363163910.1053/gast.2001.27028 11522747
    [Google Scholar]
  53. CarlsonR.M. VavrickaS.R. ElorantaJ.J. fMLP induces Hsp27 expression, attenuates NF-κB activation, and confers intestinal epithelial cell protection.Am. J. Physiol. Gastrointest. Liver Physiol.20072924G1070G107810.1152/ajpgi.00417.2006 17185631
    [Google Scholar]
  54. MuschM.W. PetrofE.O. KojimaK. RenH. McKayD.M. ChangE.B. Bacterial superantigen-treated intestinal epithelial cells upregulate heat shock proteins 25 and 72 and are resistant to oxidant cytotoxicity.Infect. Immun.20047263187319410.1128/IAI.72.6.3187‑3194.2004 15155620
    [Google Scholar]
  55. PetrofE.O. MuschM.W. CiancioM. Flagellin is required for salmonella-induced expression of heat shock protein Hsp25 in intestinal epithelium.Am. J. Physiol. Gastrointest. Liver Physiol.20082943G808G81810.1152/ajpgi.00362.2007 18202113
    [Google Scholar]
  56. LeblondC.P. The life history of cells in renewing systems.Am. J. Anat.1981160211315810.1002/aja.1001600202 6168194
    [Google Scholar]
  57. KaserA. LeeA.H. FrankeA. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease.Cell2008134574375610.1016/j.cell.2008.07.021 18775308
    [Google Scholar]
  58. HagiwaraC. TanakaM. KudoH. Increase in colorectal epithelial apoptotic cells in patients with ulcerative colitis ultimately requiring surgery.J. Gastroenterol. Hepatol.200217775876410.1046/j.1440‑1746.2002.02791.x 12121505
    [Google Scholar]
  59. GüntherC. NeumannH. NeurathM.F. BeckerC. Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium.Gut20136271062107110.1136/gutjnl‑2011‑301364 22689519
    [Google Scholar]
  60. CoskunM. Intestinal epithelium in inflammatory bowel disease.Front. Med.201412410.3389/fmed.2014.00024 25593900
    [Google Scholar]
  61. SamoilăI. DinescuS. CostacheM. Interplay between cellular and molecular mechanisms underlying inflammatory bowel diseases development—A focus on Ulcerative colitis.Cells202097164710.3390/cells9071647 32659925
    [Google Scholar]
  62. PottenC.S. GandaraR. MahidaY.R. LoefflerM. WrightN.A. The stem cells of small intestinal crypts: Where are they?Cell Prolif.200942673175010.1111/j.1365‑2184.2009.00642.x 19788585
    [Google Scholar]
  63. NunesT. BernardazziC. de SouzaH.S. Cell death and inflammatory bowel diseases: Apoptosis, necrosis, and autophagy in the intestinal epithelium.BioMed Res. Int.2014201411210.1155/2014/218493 25126549
    [Google Scholar]
  64. CrosnierC. StamatakiD. LewisJ. Organizing cell renewal in the intestine: Stem cells, signals and combinatorial control.Nat. Rev. Genet.20067534935910.1038/nrg1840 16619050
    [Google Scholar]
  65. van der FlierL.G. CleversH. Stem cells, self-renewal, and differentiation in the intestinal epithelium.Annu. Rev. Physiol.200971124126010.1146/annurev.physiol.010908.163145 18808327
    [Google Scholar]
  66. EdelblumK.L. YanF. YamaokaT. PolkB.D. Regulation of apoptosis during homeostasis and disease in the intestinal epithelium.Inflamm. Bowel Dis.200612541342410.1097/01.MIB.0000217334.30689.3e 16670531
    [Google Scholar]
  67. Di SabatinoA. CiccocioppoR. LuinettiO. Increased enterocyte apoptosis in inflamed areas of Crohn’s disease.Dis. Colon Rectum200346111498150710.1007/s10350‑004‑6802‑z 14605569
    [Google Scholar]
  68. SouzaH.S.P. TortoriC.J.A. Castelo-BrancoM.T.L. Apoptosis in the intestinal mucosa of patients with inflammatory bowel disease: evidence of altered expression of FasL and perforin cytotoxic pathways.Int. J. Colorectal Dis.200520327728610.1007/s00384‑004‑0639‑8 15503066
    [Google Scholar]
  69. BeereH.M. Death versus survival: Functional interaction between the apoptotic and stress-inducible heat shock protein pathways.J. Clin. Invest.2005115102633263910.1172/JCI26471 16200196
    [Google Scholar]
  70. ZhangS. SunY. YuanZ. Heat shock protein 90β inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt.BMB Rep.2013461475210.5483/BMBRep.2013.46.1.037 23351384
    [Google Scholar]
  71. McConnellK.W. FoxA.C. ClarkA.T. The role of heat shock protein 70 in mediating age-dependent mortality in sepsis.J. Immunol.201118663718372510.4049/jimmunol.1003652 21296977
    [Google Scholar]
  72. ZhangY. WangX. WangS. Heat shock protein 27 regulates the inflammatory response of intestinal epithelial cells by the nuclear factor-κb pathway.Dig. Dis. Sci.202065123514352010.1007/s10620‑020‑06074‑z 32078087
    [Google Scholar]
  73. BurressG.C. MuschM.W. JurivichD.A. WelkJ. ChangE.B. Effects of mesalamine on the hsp72 stress response in rat IEC-18 intestinal epithelial cells.Gastroenterology199711351474147910.1053/gast.1997.v113.pm9352849 9352849
    [Google Scholar]
  74. UrayamaS. MuschM.W. RetskyJ. MadonnaM.B. StrausD. ChangE.B. Dexamethasone protection of rat intestinal epithelial cells against oxidant injury is mediated by induction of heat shock protein 72.J. Clin. Invest.1998102101860186510.1172/JCI2235 9819372
    [Google Scholar]
  75. OtaniT. FuruseM. Tight junction structure and function revisited.Trends Cell Biol.2020301080581710.1016/j.tcb.2020.08.004 32891490
    [Google Scholar]
  76. HorowitzA. ParedesC.S.D. HaestX. TurnerJ.R. Paracellular permeability and tight junction regulation in gut health and disease.Nat. Rev. Gastroenterol. Hepatol.202320741743210.1038/s41575‑023‑00766‑3 37186118
    [Google Scholar]
  77. WangY. LinF. ZhuX. Distinct roles of intracellular heat shock protein 70 in maintaining gastrointestinal homeostasis.Am. J. Physiol. Gastrointest. Liver Physiol.20183142G164G17810.1152/ajpgi.00208.2017 29051186
    [Google Scholar]
  78. DokladnyK. MoseleyP.L. MaT.Y. Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability.Am. J. Physiol. Gastrointest. Liver Physiol.20062902G204G21210.1152/ajpgi.00401.2005 16407590
    [Google Scholar]
  79. MuschM.W. SugiK. StrausD. ChangE.B. Heat-shock protein 72 protects against oxidant-induced injury of barrier function of human colonic epithelial Caco2/bbe cells.Gastroenterology1999117111512210.1016/S0016‑5085(99)70557‑3 10381917
    [Google Scholar]
  80. LiedelJ.L. GuoY. YuY. Mother’s milk-induced Hsp70 expression preserves intestinal epithelial barrier function in an immature rat pup model.Pediatr. Res.2011695 Part 139540010.1203/PDR.0b013e3182114ec9 21263375
    [Google Scholar]
  81. LiuB. StaronM. HongF. Essential roles of grp94 in gut homeostasis via chaperoning canonical Wnt pathway.Proc. Natl. Acad. Sci.2013110176877688210.1073/pnas.1302933110 23572575
    [Google Scholar]
  82. AngeliniG. Castagneto-GisseyL. SalinariS. Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis.Nat. Commun.2022131771510.1038/s41467‑022‑35310‑5 36513656
    [Google Scholar]
  83. MaloyK.J. PowrieF. Intestinal homeostasis and its breakdown in inflammatory bowel disease.Nature2011474735129830610.1038/nature10208 21677746
    [Google Scholar]
  84. NeurathM.F. Cytokines in inflammatory bowel disease.Nat. Rev. Immunol.201414532934210.1038/nri3661 24751956
    [Google Scholar]
  85. FriedrichM. PohinM. PowrieF. Cytokine networks in the pathophysiology of inflammatory bowel disease.Immunity2019504992100610.1016/j.immuni.2019.03.017 30995511
    [Google Scholar]
  86. GenaroL.M. GomesL.E.M. FranceschiniA.P.M.F. Anti-TNF therapy and immunogenicity in inflammatory bowel diseases: A translational approach.Am. J. Transl. Res.202113121391613930 35035733
    [Google Scholar]
  87. ReineckerH-C. SteffenM. WitthoeftT. Enhand secretion of tumour necrosis factor-alpha, IL-6, and IL-1β by isolated lamina ropria monouclear cells from patients with ulcretive cilitis and Crohn’s disease.Clin. Exp. Immunol.200894117418110.1111/j.1365‑2249.1993.tb05997.x 8403503
    [Google Scholar]
  88. BasuS. BinderR.J. SutoR. AndersonK.M. SrivastavaP.K. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway.Int. Immunol.200012111539154610.1093/intimm/12.11.1539 11058573
    [Google Scholar]
  89. LiM.C. HeS.H. IL-10 and its related cytokines for treatment of inflammatory bowel disease.World J. Gastroenterol.200410562062510.3748/wjg.v10.i5.620 14991925
    [Google Scholar]
  90. CollinsC.B. AherneC.M. YeckesA. Inhibition of N-terminal ATPase on HSP90 attenuates colitis through enhanced Treg function.Mucosal Immunol.20136596097110.1038/mi.2012.134 23321985
    [Google Scholar]
  91. VenkatramanA. RamakrishnaB.S. ShajiR.V. KumarN.S.N. PulimoodA. PatraS. Amelioration of dextran sulfate colitis by butyrate: Role of heat shock protein 70 and NF-κB.Am. J. Physiol. Gastrointest. Liver Physiol.20032851G177G18410.1152/ajpgi.00307.2002 12637250
    [Google Scholar]
  92. TomaselloG. SciuméC. RappaF. Hsp10, Hsp70, and Hsp90 immunohistochemical levels change in ulcerative colitis after therapy.Eur. J. Histochem.2011554e3810.4081/ejh.2011.e38 22297444
    [Google Scholar]
  93. UlmanskyR. LandsteinD. MoallemE. A humanized monoclonal antibody against heat shock protein 60 suppresses murine arthritis and colitis and skews the cytokine balance toward an anti-inflammatory response.J. Immunol.2015194115103510910.4049/jimmunol.1500023 25904550
    [Google Scholar]
  94. TanakaK.I. NambaT. AraiY. Genetic evidence for a protective role for heat shock factor 1 and heat shock protein 70 against colitis.J. Biol. Chem.200728232232402325210.1074/jbc.M704081200 17556362
    [Google Scholar]
  95. XuW. GuoY. HuangZ. Small heat shock protein CRYAB inhibits intestinal mucosal inflammatory responses and protects barrier integrity through suppressing IKKβ activity.Mucosal Immunol.20191261291130310.1038/s41385‑019‑0198‑5 31481750
    [Google Scholar]
  96. RopeleskiM.J. TangJ. Walsh-ReitzM.M. MuschM.W. ChangE.B. Interleukin-11-induced heat shock protein 25 confers intestinal epithelial-specific cytoprotection from oxidant stress.Gastroenterology200312451358136810.1016/S0016‑5085(03)00282‑8 12730876
    [Google Scholar]
  97. HonzawaY. NakaseH. ShiokawaM. Involvement of interleukin-17A-induced expression of heat shock protein 47 in intestinal fibrosis in Crohn’s disease.Gut201463121902191210.1136/gutjnl‑2013‑305632 24534724
    [Google Scholar]
  98. HuS. CiancioM.J. LahavM. Translational inhibition of colonic epithelial heat shock proteins by IFN-gamma and TNF-alpha in intestinal inflammation.Gastroenterology200713361893190410.1053/j.gastro.2007.09.026 18054561
    [Google Scholar]
  99. WellsJ.M. RossiO. MeijerinkM. Epithelial crosstalk at the microbiota-mucosal interface.Proc. Natl. Acad. Sci. 2011108S14607461410.1073/pnas.1000092107
    [Google Scholar]
  100. FukataM. ArditiM. The role of pattern recognition receptors in intestinal inflammation.Mucosal Immunol.20136345146310.1038/mi.2013.13 23515136
    [Google Scholar]
  101. MottaV. SoaresF. SunT. PhilpottD.J. NOD-like receptors: Versatile cytosolic sentinels.Physiol. Rev.201595114917810.1152/physrev.00009.2014 25540141
    [Google Scholar]
  102. HugotJ.P. ChamaillardM. ZoualiH. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease.Nature2001411683759960310.1038/35079107 11385576
    [Google Scholar]
  103. OguraY. BonenD.K. InoharaN. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease.Nature2001411683760360610.1038/35079114 11385577
    [Google Scholar]
  104. HugotJ.P. ZaccariaI. CavanaughJ. Prevalence of CARD15/NOD2 mutations in Caucasian healthy people.Am. J. Gastroenterol.200710261259126710.1111/j.1572‑0241.2007.01149.x 17319929
    [Google Scholar]
  105. ShawM.H. KamadaN. WarnerN. KimY.G. NuñezG. The ever-expanding function of NOD2: Autophagy, viral recognition, and T cell activation.Trends Immunol.2011322737910.1016/j.it.2010.12.007 21251876
    [Google Scholar]
  106. NoguchiE. HommaY. KangX. NeteaM.G. MaX. A Crohn’s disease–associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1.Nat. Immunol.200910547147910.1038/ni.1722 19349988
    [Google Scholar]
  107. LeeK.H. BiswasA. LiuY.J. KobayashiK.S. Proteasomal degradation of Nod2 protein mediates tolerance to bacterial cell wall components.J. Biol. Chem.201228747398003981110.1074/jbc.M112.410027 23019338
    [Google Scholar]
  108. MohananV. GrimesC.L. The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease.J. Biol. Chem.201428927189871899810.1074/jbc.M114.557686 24790089
    [Google Scholar]
  109. VillaniA.C. LemireM. FortinG. Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility.Nat. Genet.2009411717610.1038/ng.285 19098911
    [Google Scholar]
  110. ZhenY. ZhangH. NLRP3 inflammasome and inflammatory bowel disease.Front. Immunol.20191027610.3389/fimmu.2019.00276 30873162
    [Google Scholar]
  111. ChouW.C. JhaS. LinhoffM.W. TingJ.P-Y. The NLR gene family: From discovery to present day.Nat. Rev. Immunol.2023231063565410.1038/s41577‑023‑00849‑x
    [Google Scholar]
  112. ChenX. LiuG. YuanY. WuG. WangS. YuanL. NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF-κB signaling.Cell Death Dis.2019101290610.1038/s41419‑019‑2157‑1 31787755
    [Google Scholar]
  113. MaoL. KitaniA. SimilukM. Loss-of-function CARD8 mutation causes NLRP3 inflammasome activation and Crohn’s disease.J. Clin. Invest.201812851793180610.1172/JCI98642 29408806
    [Google Scholar]
  114. LiuL. DongY. YeM. The pathogenic role of NLRP3 inflammasome activation in inflammatory bowel diseases of both mice and humans.J. Crohn’s Colitis201711673775010.1093/ecco‑jcc/jjw219 27993998
    [Google Scholar]
  115. ZakiM.H. BoydK.L. VogelP. KastanM.B. LamkanfiM. KannegantiT.D. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis.Immunity201032337939110.1016/j.immuni.2010.03.003 20303296
    [Google Scholar]
  116. UmikerB. LeeH.H. CopeJ. The NLRP3 inflammasome mediates DSS-induced intestinal inflammation in Nod2 knockout mice.Innate Immun.201925213214310.1177/1753425919826367 30774010
    [Google Scholar]
  117. SaberS. Abd El-KaderE.M. SharafH. Celastrol augments sensitivity of NLRP3 to CP-456773 by modulating HSP-90 and inducing autophagy in dextran sodium sulphate-induced colitis in rats.Toxicol. Appl. Pharmacol.202040011507510.1016/j.taap.2020.115075 32470352
    [Google Scholar]
  118. LeeA. De MeiC. FereiraM. Dexamethasone-loaded polymeric nanoconstructs for monitoring and treating inflammatory bowel disease.Theranostics20177153653366610.7150/thno.18183 29109767
    [Google Scholar]
  119. IacucciM. de SilvaS. GhoshS. Mesalazine in inflammatory bowel disease: A trendy topic once again?Can. J. Gastroenterol.201024212713310.1155/2010/586092 20151072
    [Google Scholar]
  120. OhkawaraT. TakedaH. NishiwakiM. NishihiraJ. AsakaM. Protective effects of heat shock protein 70 induced by geranylgeranylacetone on oxidative injury in rat intestinal epithelial cells.Scand. J. Gastroenterol.200641331231710.1080/00365520500319427 16497619
    [Google Scholar]
  121. QinY. NaitoY. HandaO. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.J. Clin. Biochem. Nutr.201149317418110.3164/jcbn.11‑26 22128216
    [Google Scholar]
  122. ZhangX. XuY. FanM. Ponicidin-induced conformational changes of HSP90 regulates the MAPK pathway to relieve ulcerative colitis.J. Ethnopharmacol.202432111748310.1016/j.jep.2023.117483 38008273
    [Google Scholar]
  123. OhkawaraT. NishihiraJ. NagashimaR. TakedaH. AsakaM. Polaprezinc protects human colon cells from oxidative injury induced by hydrogen peroxide: Relevant to cytoprotective heat shock proteins.World J. Gastroenterol.200612386178618110.3748/wjg.v12.i38.6178 17036391
    [Google Scholar]
  124. CollinsC.B. StrassheimD. AherneC.M. YeckesA.R. JedlickaP. de ZoetenE.F. Targeted inhibition of heat shock protein 90 suppresses tumor necrosis factor-α and ameliorates murine intestinal inflammation.Inflamm. Bowel Dis.201420468569410.1097/01.MIB.0000442839.28664.75 24552830
    [Google Scholar]
  125. CalderwoodS.K. GongJ. Heat shock proteins promote cancer: It’s a protection racket.Trends Biochem. Sci.201641431132310.1016/j.tibs.2016.01.003 26874923
    [Google Scholar]
  126. Abi ZamerB. El-HuneidiW. EladlM.A. MuhammadJ.S. Ins and outs of heat shock proteins in colorectal carcinoma: Its role in carcinogenesis and therapeutic perspectives.Cells20211011286210.3390/cells10112862 34831085
    [Google Scholar]
  127. BerthenetK. BokhariA. LagrangeA. HSP110 promotes colorectal cancer growth through STAT3 activation.Oncogene201736162328233610.1038/onc.2016.403 27819670
    [Google Scholar]
  128. BerthenetK. BoudescoC. ColluraA. Extracellular HSP110 skews macrophage polarization in colorectal cancer.OncoImmunology201657e117026410.1080/2162402X.2016.1170264 27622020
    [Google Scholar]
  129. SantosL.S. SilvaV.R. de CastroM.V.L. New ruthenium-xanthoxylin complex eliminates colorectal cancer stem cells by targeting the heat shock protein 90 chaperone.Cell Death Dis.2023141283210.1038/s41419‑023‑06330‑w 38102125
    [Google Scholar]
  130. SunY. XiaoW. YuY. Colorectal cancer-derived extracellular vesicles containing HSP70 enhance macrophage phagocytosis by up-regulating MARCO expression.Exp. Cell Res.2023426211356510.1016/j.yexcr.2023.113565 36958650
    [Google Scholar]
  131. AlsaabH.O. AlmalkiA.H. Anti-HSP70 alleviates cell migration and proliferation in colorectal cancer cells (CRC) by targeting CXCR4 (in vitro study).Med. Oncol.202340925610.1007/s12032‑023‑02122‑6 37516711
    [Google Scholar]
  132. GuoJ. ZhuS. DengH. XuR. HSP60 knockdown suppresses proliferation in colorectal cancer cells via activating the adenine/AMPK/mTOR signaling pathway.Oncol. Lett.202122263010.3892/ol.2021.12891 34267822
    [Google Scholar]
  133. YuZ. ZhiJ. PengX. ZhongX. XuA. Clinical significance of HSP27 expression in colorectal cancer.Mol. Med. Rep.201036953958 21472339
    [Google Scholar]
  134. WangF. ZhangP. ShiC. YangY. QinH. Immunohistochemical detection of HSP27 and hnRNP K as prognostic and predictive biomarkers for colorectal cancer.Med. Oncol.20122931780178810.1007/s12032‑011‑0037‑3 21861207
    [Google Scholar]
  135. GarridoC. OttaviP. FromentinA. HSP27 as a mediator of confluence-dependent resistance to cell death induced by anticancer drugs.Cancer Res.1997571326612667 9205074
    [Google Scholar]
  136. EadenJ.A. AbramsK.R. MayberryJ.F. The risk of colorectal cancer in ulcerative colitis: A meta-analysis.Gut200148452653510.1136/gut.48.4.526 11247898
    [Google Scholar]
  137. ArakiK. MikamiT. YoshidaT. High expression of HSP47 in ulcerative colitis-associated carcinomas: proteomic approach.Br. J. Cancer2009101349249710.1038/sj.bjc.6605163 19603022
    [Google Scholar]
  138. BurmerG.C. RabinovitchP.S. HaggittR.C. Neoplastic progression in ulcerative colitis: Histology, DNA content, and loss of a p53 allele.Gastroenterology199210351602161010.1016/0016‑5085(92)91184‑6 1358743
    [Google Scholar]
  139. YinJ. HarpazN. TongY. p53 Point mutations in dysplastic and cancerous ulcerative colitis lesions.Gastroenterology199310461633163910.1016/0016‑5085(93)90639‑T 8500720
    [Google Scholar]
  140. CooksT. PaterasI.S. TarcicO. Mutant p53 prolongs NF-κB activation and promotes chronic inflammation and inflammation-associated colorectal cancer.Cancer Cell201323563464610.1016/j.ccr.2013.03.022 23680148
    [Google Scholar]
  141. LiD. MarchenkoN.D. MollU.M. SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis.Cell Death Differ.201118121904191310.1038/cdd.2011.71 21637290
    [Google Scholar]
  142. Schulz-HeddergottR. StarkN. EdmundsS.J. Therapeutic ablation of gain-of-function mutant p53 in colorectal cancer inhibits stat3-mediated tumor growth and invasion.Cancer Cell2018342298314.e710.1016/j.ccell.2018.07.004 30107178
    [Google Scholar]
  143. GestlE.E. BöttgerA.S. Cytoplasmic sequestration of the tumor suppressor p53 by a heat shock protein 70 family member, mortalin, in human colorectal adenocarcinoma cell lines.Biochem. Biophys. Res. Commun.2012423241141610.1016/j.bbrc.2012.05.139 22683628
    [Google Scholar]
  144. BinderR.J. Immunosurveillance of cancer and the heat shock protein-CD91 pathway.Cell. Immunol.201934310381410.1016/j.cellimm.2018.05.007 29784128
    [Google Scholar]
  145. OuraJ. TamuraY. KamiguchiK. Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells.Int. Immunol.201123422323710.1093/intimm/dxq475 21421737
    [Google Scholar]
  146. IchiyanagiT. ImaiT. KajiwaraC. Essential role of endogenous heat shock protein 90 of dendritic cells in antigen cross-presentation.J. Immunol.201018552693270010.4049/jimmunol.1000821 20668218
    [Google Scholar]
  147. ImaiT. KatoY. KajiwaraC. Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells.Proc. Natl. Acad. Sci.201110839163631636810.1073/pnas.1108372108 21930907
    [Google Scholar]
  148. BendzH. RuhlandS.C. PandyaM.J. Human heat shock protein 70 enhances tumor antigen presentation through complex formation and intracellular antigen delivery without innate immune signaling.J. Biol. Chem.200728243316883170210.1074/jbc.M704129200 17684010
    [Google Scholar]
  149. XieJ. ZhuH. GuoL. Lectin-like oxidized low-density lipoprotein receptor-1 delivers heat shock protein 60-fused antigen into the MHC class I presentation pathway.J. Immunol.201018542306231310.4049/jimmunol.0903214 20631313
    [Google Scholar]
  150. PeetermansW.E. D’HaensG.R. CeuppensJ.L. RutgeertsP. GeboesK. Mucosal expression by B7-positive cells of the 60-kilodalton heat-shock protein in inflammatory bowel disease.Gastroenterology19951081758210.1016/0016‑5085(95)90010‑1 7528700
    [Google Scholar]
  151. TomaselloG. RodolicoV. ZerilliM. Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic role of Hsp60 in ulcerative colitis.Appl. Immunohistochem. Mol. Morphol.201119655256110.1097/PAI.0b013e3182118e5f 21441812
    [Google Scholar]
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  • Article Type:
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Keyword(s): CD; epithelial barrier; HSP; IBD; immune system; microbiota; UC
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