Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Molecular Medicine
  4. Volume 24, Issue 11
  5. Article
Volume 24, Issue 11
  • ISSN: 1566-5240
  • E-ISSN:

Abstract

Background

Airway remodeling is one of the reasons for severe steroid-resistant asthma related to HMGB1/RAGE signaling or Th17 immunity.

Objective

Our study aims to investigate the relationship between the HMGB1/RAGE signaling and the Th17/IL-17 signaling in epithelial-mesenchymal transformation (EMT) of airway remodeling.

Methods

CD4+ T lymphocytes were collected from C57 mice. CD4+ T cell and Th17 cell ratio was analyzed by flow cytometry. IL-17 level was detected by ELISA. The E-cadherin and α-SMA were analyzed by RT-qPCR and immunohistochemistry. The E-cadherin, α-SMA, and p-Smad3 expression were analyzed by western blot.

Results

The HMGB1/RAGE signaling promoted the differentiation and maturation of Th17 cells in a dose-dependent manner . The HMGB1/RAGE signaling also promoted the occurrence of bronchial EMT. The EMT of bronchial epithelial cells was promoted by Th17/IL-17 and the HMGB1 treatment in a synergic manner. Silencing of RAGE reduced the signaling transduction of HMGB1 and progression of bronchial EMT.

Conclusion

HMGB1/RAGE signaling synergistically enhanced TGF-β1-induced bronchial EMT by promoting the differentiation of Th17 cells and the secretion of IL-17.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240249953231024060610
2023-10-27
2024-11-30

  • From This Site

    /content/journals/cmm/10.2174/0115665240249953231024060610
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. BousquetJ. DahlR. KhaltaevN. Global alliance against chronic respiratory diseases.Pneumonol. Alergol. Pol.2008763160169
     [Google Scholar]
  2. HackettT.L. Epithelial–mesenchymal transition in the pathophysiology of airway remodelling in asthma.Curr. Opin. Allergy Clin. Immunol.2012121535910.1097/ACI.0b013e32834ec6eb 22217512
     [Google Scholar]
  3. HackettT.L. WarnerS.M. StefanowiczD. Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-beta1.Am. J. Respir. Crit. Care Med.2009180212213310.1164/rccm.200811‑1730OC 19406982
     [Google Scholar]
  4. KolosovaI. NetheryD. KernJ.A. Role of Smad2/3 and p38 MAP kinase in TGF-β1-induced epithelial-mesenchymal transition of pulmonary epithelial cells.J. Cell. Physiol.201122651248125410.1002/jcp.22448 20945383
     [Google Scholar]
  5. BergeronC. TulicM.K. HamidQ. Airway remodelling in asthma: From benchside to clinical practice.Can. Respir. J.2010174e85e9310.1155/2010/318029 20808979
     [Google Scholar]
  6. BaiT.R. Evidence for airway remodeling in chronic asthma.Curr. Opin. Allergy Clin. Immunol.2010101828610.1097/ACI.0b013e32833363b2 19858714
     [Google Scholar]
  7. CavoneL. CuppariC. MantiS. Increase in the level of proinflammatory cytokine hmgb1 in nasal fluids of patients with rhinitis and its sequestration by glycyrrhizin induces eosinophil cell death.Clin. Exp. Otorhinolaryngol.20158212312810.3342/ceo.2015.8.2.123 26045910
     [Google Scholar]
  8. UllahM.A. LohZ. GanW.J. Receptor for advanced glycation end products and its ligand high-mobility group box-1 mediate allergic airway sensitization and airway inflammation.J. Allergy Clin. Immunol.20141342440450.e310.1016/j.jaci.2013.12.1035 24506934
     [Google Scholar]
  9. HudsonB.I. LippmanM.E. Targeting RAGE signaling in inflammatory disease.Annu. Rev. Med.201869134936410.1146/annurev‑med‑041316‑085215 29106804
     [Google Scholar]
  10. XieJ. MéndezJ.D. Méndez-ValenzuelaV. Aguilar-HernándezM.M. Cellular signalling of the receptor for advanced glycation end products (RAGE).Cell. Signal.201325112185219710.1016/j.cellsig.2013.06.013 23838007
     [Google Scholar]
  11. ZengS. FeirtN. GoldsteinM. Blockade of receptor for advanced glycation end product (RAGE) attenuates ischemia and reperfusion injury to the liver in mice.Hepatology200439242243210.1002/hep.20045 14767995
     [Google Scholar]
  12. RepapiE. SayersI. WainL.V. Genome-wide association study identifies five loci associated with lung function.Nat. Genet.2010421364410.1038/ng.501 20010834
     [Google Scholar]
  13. OuyangF. HuangH. ZhangM. HMGB1 induces apoptosis and EMT in association with increased autophagy following H/R injury in cardiomyocytes.Int. J. Mol. Med.201637367968910.3892/ijmm.2016.2474 26847839
     [Google Scholar]
  14. ChoyD.F. HartK.M. BorthwickL.A. T H 2 and T H 17 inflammatory pathways are reciprocally regulated in asthma.Sci. Transl. Med.20157301301ra12910.1126/scitranslmed.aab3142 26290411
     [Google Scholar]
  15. Margelidon-CozzolinoV. TsicopoulosA. ChenivesseC. de NadaiP. Role of Th17 cytokines in airway remodeling in asthma and therapy perspectives.Front. Allergy2022380639110.3389/falgy.2022.806391 35386663
     [Google Scholar]
  16. SilvaM.J. de SantanaM.B.R. TostaB.R. Variants in the IL17 pathway genes are associated with atopic asthma and atopy makers in a South American population.Allergy Asthma Clin. Immunol.20191512810.1186/s13223‑019‑0340‑7 31168303
     [Google Scholar]
  17. JiX. LiJ. XuL. IL4 and IL-17A provide a Th2/Th17-polarized inflammatory milieu in favor of TGF-β1 to induce bronchial epithelial-mesenchymal transition (EMT).Int. J. Clin. Exp. Pathol.20136814811492 23923066
     [Google Scholar]
  18. HeZ. ShotorbaniS.S. JiaoZ. HMGB1 promotes the differentiation of Th17 via up-regulating TLR2 and IL-23 of CD14+ monocytes from patients with rheumatoid arthritis.Scand. J. Immunol.201276548349010.1111/j.1365‑3083.2012.02759.x 22809173
     [Google Scholar]
  19. LiR. WangJ. ZhuF. HMGB1 regulates T helper 2 and T helper17 cell differentiation both directly and indirectly in asthmatic mice.Mol. Immunol.201897455510.1016/j.molimm.2018.02.014 29567318
     [Google Scholar]
  20. MaL. ZengJ. MoB. High mobility group box 1: A novel mediator of Th2-type response-induced airway inflammation of acute allergic asthma.J. Thorac. Dis.201571017321741 26623095
     [Google Scholar]
  21. JiangY. LiL. PanQ. Methyl-cpg-binding domain protein 2 silencing inhibits Th17 differentiation of CD4+T cells induced by ovalbumin.Iran. J. Immunol.20232014556 36932919
     [Google Scholar]
  22. HouC. KongJ. LiangY. HMGB1 contributes to allergen-induced airway remodeling in a murine model of chronic asthma by modulating airway inflammation and activating lung fibroblasts.Cell. Mol. Immunol.201512440942310.1038/cmi.2014.60 25152078
     [Google Scholar]
  23. KanazawaH. TochinoY. AsaiK. IchimaruY. WatanabeT. HirataK. Validity of HMGB1 measurement in epithelial lining fluid in patients with COPD.Eur. J. Clin. Invest.201242441942610.1111/j.1365‑2362.2011.02598.x 21950682
     [Google Scholar]
  24. HuangL. YaoY. ShengZ. Novel insights for high mobility group box 1 protein-mediated cellular immune response in sepsis:A systemic review.World J. Emerg. Med.20123316517110.5847/wjem.j.issn.1920‑8642.2012.03.001 25215057
     [Google Scholar]
  25. GongS. LiJ. MaL. Blockade of dopamine D1-like receptor signalling protects mice against OVA-induced acute asthma by inhibiting B-cell activating transcription factor signalling and Th17 function.FEBS J.2013280236262627310.1111/febs.12549 24112622
     [Google Scholar]
  26. ZhangL. LiK. Bing MaL. Effects and mechanism of arsenic trioxide on reversing the asthma pathologies including Th17-IL-17 axis in a mouse model.Iran. J. Allergy Asthma Immunol.2012112133145 22761187
     [Google Scholar]
  27. American Thoracic Society. Idiopathic pulmonary fibrosis: Diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS).Am. J. Respir. Crit. Care Med.20001612 Pt 1646664 10673212
     [Google Scholar]
  28. LiangY. HouC. KongJ. HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2.Mol. Cell. Biochem.20154051-2637110.1007/s11010‑015‑2396‑0 25862459
     [Google Scholar]
  29. FerhaniN. LetuveS. KozhichA. Expression of high-mobility group box 1 and of receptor for advanced glycation end products in chronic obstructive pulmonary disease.Am. J. Respir. Crit. Care Med.2010181991792710.1164/rccm.200903‑0340OC 20133931
     [Google Scholar]
  30. MoreauJ.M. VelegrakiM. BolyardC. RosenblumM.D. LiZ. Transforming growth factor–β1 in regulatory T cell biology.Sci. Immunol.2022769eabi461310.1126/sciimmunol.abi4613 35302863
     [Google Scholar]
  31. PalumboR. GalvezB.G. PusterlaT. Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-κB activation.J. Cell Biol.20071791334010.1083/jcb.200704015 17923528
     [Google Scholar]
  32. WangQ. LiH. YaoY. XiaD. ZhouJ. The overexpression of heparin-binding epidermal growth factor is responsible for Th17-induced airway remodeling in an experimental asthma model.J. Immunol.2010185283484110.4049/jimmunol.0901490 20530256
     [Google Scholar]
  33. LiL.L. DaiB. SunY.H. ZhangT.T. The activation of IL-17 signaling pathway promotes pyroptosis in pneumonia-induced sepsis.Ann. Transl. Med.202081167410.21037/atm‑19‑1739 32617294
     [Google Scholar]
  34. KillianK.N. KosanovichJ.L. LippM.A. EmpeyK.M. OuryT.D. PerkinsT.N. RAGE contributes to allergen driven severe neutrophilic airway inflammation via NLRP3 inflammasome activation in mice.Front. Immunol.202314103999710.3389/fimmu.2023.1039997 36776857
     [Google Scholar]
  35. ChenY. AkiravE.M. ChenW. RAGE ligation affects T cell activation and controls T cell differentiation.J. Immunol.200818164272427810.4049/jimmunol.181.6.4272 18768885
     [Google Scholar]
  36. SuC.L. ChouH.C. HuangL.T. YehT.F. ChenC.M. Combined effects of maternal inflammation and neonatal hyperoxia on lung fibrosis and RAGE expression in newborn rats.Pediatr. Res.201475227328010.1038/pr.2013.222 24226635
     [Google Scholar]
  37. ZhangF. SuX. HuangG. sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells.Sci. Rep.2017711426810.1038/s41598‑017‑14667‑4 29079726
     [Google Scholar]
  38. ZhangF. HuangG. HuB. Anti-HMGB1 neutralizing antibody ameliorates neutrophilic airway inflammation by suppressing dendritic cell-mediated Th17 polarization.Mediators Inflamm.2014201411110.1155/2014/257930 24959003
     [Google Scholar]
  39. ZhangF. HuangG. HuB. QianG. SongY. Recombinant HMGB1 A box protein inhibits Th17 responses in mice with neutrophilic asthma by suppressing dendritic cell-mediated Th17 polarization.Int. Immunopharmacol.201524111011810.1016/j.intimp.2014.11.005 25479722
     [Google Scholar]
  40. XingY. ChengD. ShiC. ShenZ. The protective role of YTHDF1-knock down macrophages on the immune paralysis of severe sepsis rats with ECMO.Microvasc. Res.202113710417810.1016/j.mvr.2021.104178 34015275
     [Google Scholar]
  41. ArikkattJ. UllahM.A. ShortK.R. RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma.eLife20176e2119910.7554/eLife.21199 28099113
     [Google Scholar]
  42. NesiR.T. Kennedy-FeitosaE. LanzettiM. Inflammatory and oxidative stress markers in experimental allergic asthma.Inflammation20174041166117610.1007/s10753‑017‑0560‑2 28391514
     [Google Scholar]
  43. StrohbueckerL. KoenenH. van RijssenE. Increased dermal expression of chromatin-associated protein HMGB1 and concomitant T-cell expression of the DNA RAGE in patients with psoriasis vulgaris.Psoriasis2019971710.2147/PTT.S190507 30859087
     [Google Scholar]
  44. HeR. ChenY. ChenX. YuanB. Mechanism of miR-181a-5p in regulatory T/T-Helper 17 immune imbalance and asthma development in mice with allergic rhinitis.Int. Arch. Allergy Immunol.2022183437538810.1159/000519703 34942624
     [Google Scholar]
/content/journals/cmm/10.2174/0115665240249953231024060610
Loading
HMGB1/RAGE Signaling Regulates Th17/IL-17 and Its Role in Bronchial Epithelial-Mesenchymal Transformation
Current Molecular Medicine 24, 1401 (2024); https://doi.org/10.2174/0115665240249953231024060610
/content/journals/cmm/10.2174/0115665240249953231024060610
/content/journals/cmm/10.2174/0115665240249953231024060610
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): airway remodeling; bronchial asthma; EMT; HMGB1; RAGE; Th17/IL-17

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test