Skip to content
2000
image of Interleukin-24: A Versatile Regulator of Wound Healing

Abstract

The skin, as the body's largest organ, is crucial for maintaining homeostasis and providing protection, making it susceptible to wounds from various causes. Wound healing is a complex process involving numerous cellular activities. Any interruptions can lead to chronic, non-healing wounds, which present significant challenges in healthcare. Interleukin-24 (IL-24), a cytokine within the IL-10 family, has become recognized for its significant role in wound healing due to its diverse effects on cellular processes. IL-24 can inhibit keratinocyte migration, potentially leading to chronic wounds, and promote endothelial cell migration and angiogenesis, which are vital for tissue repair. This dual role highlights IL-24's intricate involvement in wound healing, as it can hinder and aid different aspects of the process. Research indicates that IL-24 expression increases in response to inflammatory mediators and is involved in various immune responses, emphasizing its regulatory function. Further research on IL-24's mechanisms and interactions is essential for developing new therapeutic strategies to enhance tissue regeneration and treat chronic wounds and skin disorders. A deeper understanding of IL-24's functions could transform wound care, providing new approaches for effectively managing and treating conditions involving impaired healing.

Loading

Article metrics loading...

/content/journals/raiad/10.2174/0127722708349928250108191556
2025-01-30
2025-07-11
Loading full text...

Full text loading...

References

  1. Botek A.A. Lookingbill D.P. The structure and function of sebaceous glands. The Biology of the Skin Freinkel R.K. Woodley D.T. CRC Press 2001 432
    [Google Scholar]
  2. Kolimi P. Narala S. Nyavanandi D. Youssef A.A.A. Dudhipala N. Innovative treatment strategies to accelerate wound healing: Trajectory and recent advancements. Cells 2022 11 15 2439 10.3390/cells11152439 35954282
    [Google Scholar]
  3. Zidarič T. Kleinschek K.S. Maver U. Maver T. Introduction Springer briefs. 2023 Available from: https://typeset.io/papers/introduction-15tby36z
  4. Visha M. Karunagaran M. A review on wound healing. Int. J. Clin. Correl. 2019 3 2 50
    [Google Scholar]
  5. Broughton G. II Janis J.E. Attinger C.E. Wound healing: An overview. Plast. Reconstr. Surg. 2006 117 7 Suppl. 1e S-32e-S 10.1097/01.prs.0000222562.60260.f9 16801750
    [Google Scholar]
  6. Abazari M. Ghaffari A. Wounds H.R. A systematic review on classification, identification, and healing process of burn wound healing. Int. J. Low Extrem. Wounds. 2022 21 1 18 30 10.1177/1534734620924857
    [Google Scholar]
  7. Sorg H. Tilkorn D.J. Hager S. Hauser J. Mirastschijski U. Skin Wound Healing: An update on the current knowledge and concepts. Eur. Surg. Res. 2017 58 1-2 81 94 10.1159/000454919 27974711
    [Google Scholar]
  8. Monika P Chandraprabha MN Rangarajan A Waiker PV Chidambara Murthy KN Chidambara murthy kn. challenges in healing wound: role of complementary and alternative medicine. Front Nutr. 2021 8 791899 10.3389/fnut.2021.791899 35127787
    [Google Scholar]
  9. Sen C.K. Human wound and its burden: Updated 2020 compendium of estimates. Adv. Wound Care 2021 10 5 281 292 10.1089/wound.2021.0026 33733885
    [Google Scholar]
  10. Alvarez-Suarez J.M. Tulipani S. Romandini S. Bertoli E. Battino M. Contribution of honey in nutrition and human health: A review. Med. J. Nutrition Metab. 2010 3 1 15 23 10.1007/s12349‑009‑0051‑6
    [Google Scholar]
  11. Gilmore M.A. Phases of wound healing. Dimens. Oncol. Nurs. 1991 5 3 32 34 1823567
    [Google Scholar]
  12. Rodrigues M Kosaric N Bonham CA Gurtner GC Wound healing: A cellular perspective Physiol Rev. 2019 99 1 665 706 10.1152/physrev.00067.2017 30475656
    [Google Scholar]
  13. Henry R.L. Steiman R.H. Mechanisms of hemostasis. Microvasc. Res. 1968 1 1 68 82 10.1016/0026‑2862(68)90007‑1
    [Google Scholar]
  14. Mazini L. Rochette L. Admou B. Amal S. Malka G. Hopes and limits of adipose-derived stem cells (ADSCs) and mesenchymal stem cells (MSCs) in wound healing. Int. J. Mol. Sci. 2020 21 4 1306 10.3390/ijms21041306 32075181
    [Google Scholar]
  15. Turabelidze A. Dipietro L.A. Inflammation and wound healing. Endodontics Topics John Wiley & Sons 2011 24 1 26 38 10.1111/etp.12012
    [Google Scholar]
  16. Ghaly P. Iliopoulos J. Ahmad M. The role of nutrition in wound healing: An overview. Br. J. Nurs. 2021 30 5 S38 S42 10.12968/bjon.2021.30.5.S38 33733851
    [Google Scholar]
  17. Witte M.B. Barbul A. General principles of wound healing. Surg. Clin. North Am. 1997 77 3 509 528 10.1016/S0039‑6109(05)70566‑1 9194878
    [Google Scholar]
  18. Nourian Dehkordi A Mirahmadi Babaheydari F Chehelgerdi M Raeisi Dehkordi S. Skin tissue engineering: Wound healing based on stem-cell-based therapeutic strategies Ste. Ce. Res. Ther. 2019 10 1 111 10.1186/s13287‑019‑1212‑2 30922387
    [Google Scholar]
  19. O’Kane S. Wound remodelling and scarring. J. Wound Care. 2013 11 8 296 299 10.12968/jowc.2002.11.8.26426 12360763
    [Google Scholar]
  20. Wilkinson HN Hardman MJ Wound healing: Cellular mechanisms and pathological outcomes. Open Biol. 2020 10 9 200223 10.1098/rsob.200223 32993416
    [Google Scholar]
  21. Burgess JL Wyant WA Abujamra BA Kirsner RS Jozic I Healing, inflammation, and Fibrosis: Updates in diabetic wound healing, inflammation, and scarring. Semin. Plast. Surg. 2021 57 10 1072 10.3390/medicina57101072 34684109
    [Google Scholar]
  22. Dasari N Jiang A Skochdopole A Chung J Reece EM Vorstenbosch J Healing, inflammation, and fibrosis: Updates in diabetic wound healing, inflammation, and scarring. Sem. Pla. Su. 2021 35 3 153 158 10.1055/s‑0041‑1731460 34526862
    [Google Scholar]
  23. Li Q. Hu W. Huang Q. Yang J. Li B. Ma K. MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing by targeting IRAK1. 2023 8 1 62 10.1038/s41392‑022‑01263‑w 36775818
    [Google Scholar]
  24. Liu X. Wei Q. Sun Z. Cui S. Wan X. Chu Z. Small extracellular vesicles: Yields, functionalization and applications in diabetic wound management. Interdiscip. Med. 2023 1 4 e20230019 10.1002/INMD.20230019
    [Google Scholar]
  25. Huang Q. Chu Z. Wang Z. Li Q. Meng S. Lu Y. circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models. Nat. Commun. 2024 15 3904 10.1038/s41467‑024‑48284‑3
    [Google Scholar]
  26. Lang X Li L Li Y Feng X. Effect of diabetes on wound healing: A bibliometrics and visual analysis. J. Multidiscip. Healthc. 2024 17 1275 1289 10.2147/JMDH.S457498 38524865
    [Google Scholar]
  27. Dwivedi J. Sachan P. Wal P. Wal A. Rai A.K. Current state and future perspective of diabetic wound healing treatment: Present evidence from clinical trials. Curr. Diabetes Rev. 2024 20 5 e280823220405 10.2174/1573399820666230828091708 37641999
    [Google Scholar]
  28. Zhong W. Meng H. Ma L. Wan X. Chen S. Ma K. Hydrogels loaded with MSC-derived small extracellular vesicles: A novel cell-free tissue engineering system for diabetic wound management. VIEW 2024 5 4 01 06 10.1002/VIW.20230110
    [Google Scholar]
  29. Holl J Kowalewski C Zimek Z Fiedor P Kaminski A Oldak T Cloning and Characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. 2021 J. Immunol. 164 4 1814 9 10.3390/cells10030655 10657629
    [Google Scholar]
  30. Dumoutier L. Louahed J. Renauld J.C. Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J. Immunol. 2000 164 4 1814 1819 10.4049/jimmunol.164.4.1814 10657629
    [Google Scholar]
  31. Xie M.H. Aggarwal S. Ho W.H. Foster J. Zhang Z. Stinson J. Wood W.I. Goddard A.D. Gurney A.L. Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J. Biol. Chem. 2000 275 40 31335 31339 10.1074/jbc.M005304200 10875937
    [Google Scholar]
  32. Vaid B. Chopra B.S. Raut S. Sagar A. Badmalia M.D. Antioxidant and wound healing property of gelsolin in 3T3-L1 cells. Oxid. Med. Cell Longev. 2020 2020 4045365 10.1155/2020/404536 32104532
    [Google Scholar]
  33. Pestka S. Krause C.D. Sarkar D. Walter M.R. Shi Y. Fisher P.B. I nterleukin -10 and R elated C ytokines and R eceptors. Annu. Rev. Immunol. 2004 22 1 929 979 10.1146/annurev.immunol.22.012703.104622 15032600
    [Google Scholar]
  34. Ekmekcioglu S. Ellerhorst J. Mhashilkar A.M. Sahin A.A. Read C.M. Prieto V.G. Chada S. Grimm E.A. Down-regulated melanoma differentiation associated gene (mda-7) expression in human melanomas. Int. J. Cancer 2001 94 1 54 59 10.1002/ijc.1437 11668478
    [Google Scholar]
  35. Kim K. Kim J. Kim H. Sung G.Y. Effect of α-lipoic acid on the development of human skin equivalents using a pumpless skin-on-a-chip model. Int. J. Mol. Sci. 2021 22 4 2160 10.3390/ijms22042160 33671528
    [Google Scholar]
  36. Liao S. Yang Y. Chen S. Bi Y. Huang Q. Wei Z. Qin A. Liu B. IL-24 inhibits endometrial cancer cell proliferation by promoting apoptosis through the mitochondrial intrinsic signaling pathway. Biomed. Pharmacother. 2020 124 109831 10.1016/j.biopha.2020.109831 31972354
    [Google Scholar]
  37. Roeb E. Interleukin-13 (IL-13): A pleiotropic cytokine involved in wound healing and fibrosis. Int. J. Mol. Sci. 2023 24 16 12884 10.3390/ijms241612884 37629063
    [Google Scholar]
  38. Poindexter N.J. Williams R.R. Powis G. Jen E. Caudle A.S. Chada S. Grimm E.A. IL‐24 is expressed during wound repair and inhibits TGFα‐induced migration and proliferation of keratinocytes. Exp. Dermatol. 2010 19 8 714 722 10.1111/j.1600‑0625.2010.01077.x 20545760
    [Google Scholar]
  39. Pastar I. Stojadinovic O. Yin N.C. Ramirez H. Nusbaum A.G. Sawaya A. Patel S.B. Khalid L. Isseroff R.R. Tomic-Canic M. Epithelialization in wound healing: A comprehensive review. Adv. Wound Care 2014 3 7 445 464 10.1089/wound.2013.0473 25032064
    [Google Scholar]
  40. Wang M. Tan Z. Zhang R. Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2 J. Biol. Chem. 2002 277 9 7341 7347
    [Google Scholar]
  41. Kolumam G. Wu X. Lee W.P. Hackney J.A. Zavala-Solorio J. Gandham V. Danilenko D.M. Arora P. Wang X. Ouyang W. IL-22R ligands IL-20, IL-22, and IL-24 promote wound healing in diabetic db/db mice. PLoS One 2017 12 1 e0170639 10.1371/journal.pone.0170639 28125663
    [Google Scholar]
  42. Wolk K. Haugen H.S. Xu W. Witte E. Waggie K. Anderson M. vom Baur E. Witte K. Warszawska K. Philipp S. Johnson-Leger C. Volk H.D. Sterry W. Sabat R. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-γ are not. J. Mol. Med. 2009 87 5 523 536 10.1007/s00109‑009‑0457‑0 19330474
    [Google Scholar]
  43. Kotenko S.V. The family of IL-10-related cytokines and their receptors: Related, but to what extent? Cytokine Growth Factor Rev. 2002 13 3 223 240 10.1016/S1359‑6101(02)00012‑6 12486876
    [Google Scholar]
  44. Baron J.M. Glatz M. Proksch E. Optimal support of wound healing: New insights. Dermatology 2020 236 6 593 600 10.1159/000505291 31955162
    [Google Scholar]
  45. Blumberg H. Conklin D. Xu W. Grossmann A. Brender T. Carollo S. Eagan M. Foster D. Haldeman B.A. Hammond A. Haugen H. Jelinek L. Kelly J.D. Madden K. Maurer M.F. Parrish-Novak J. Prunkard D. Sexson S. Sprecher C. Waggie K. West J. Whitmore T.E. Yao L. Kuechle M.K. Dale B.A. Chandrasekher Y.A. Interleukin 20. Cell 2001 104 1 9 19 10.1016/S0092‑8674(01)00187‑8 11163236
    [Google Scholar]
  46. Steiniche T. Kragballe K. Rømer J. Hasselager E. Nørby P.L. Thorn Clausen J. Epidermal overexpression of interleukin-19 and -20 mRNa in psoriatic skin disappears after short-term treatment with cyclosporine A or calcipotriol. J. Invest. Dermatol. 2003 121 6 1306 1311 10.1111/j.1523‑1747.2003.12626.x 14675174
    [Google Scholar]
  47. Ruthenborg RJ Ban JJ Wazir A Takeda N Kim JW Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1. Mol. Cells 2014 37 9 637 43 10.14348/molcells.2014.0150 24957212
    [Google Scholar]
  48. Luo Z. Tian M. Yang G. Tan Q. Chen Y. Li G. Hypoxia signaling in human health and diseases: Implications and prospects for therapeutics. Signal Transduct Target Ther. 2022 7 1 218 10.1038/s41392‑022‑01080‑1
    [Google Scholar]
  49. Ban E. Jeong S. Park M. Kwon H. Park J. Song E.J. Kim A. Accelerated wound healing in diabetic mice by miRNA-497 and its anti-inflammatory activity. Biomed. Pharmacother. 2020 121 109613 10.1016/j.biopha.2019.109613 31707336
    [Google Scholar]
  50. Todica M. Stefan R. Pop C.V. Papuc I. Stan O. Olar L.E. UV-VIS and fluorescence investigation of some poly(acrylic) gels. Stud. Univ. Babes-Bolyai Chem. 2015 60 1 7 17
    [Google Scholar]
  51. Dutta P.K. Tripathi S. Mehrotra G.K. Dutta J. Perspectives for chitosan based antimicrobial films in food applications. Food Chem. 2009 114 4 1173 1182 10.1016/j.foodchem.2008.11.047
    [Google Scholar]
  52. Sibbald RG Elliott JA Persaud-Jaimangal R Goodman L Armstrong DG Harley C Wound bed preparation 2021. Adv Skin Wound Care 2021 34 4 183 195 10.1097/01.ASW.0000733724.87630.d6. 33739948
    [Google Scholar]
  53. Arribas-López E. Zand N. Ojo O. Snowden M.J. Kochhar T. A systematic review of the effect of centella asiatica on wound healing. Int. J. Environ. Res. Public Health 2022 19 6 3266 10.3390/ijerph19063266 35328954
    [Google Scholar]
  54. Kwon N.H. Oh M.J. Min T.H. Lee B.J. Choi D.C. Causes and clinical features of subacute cough. Chest 2006 129 5 1142 1147 10.1378/chest.129.5.1142 16685003
    [Google Scholar]
  55. Song W.J. Chang Y.S. Faruqi S. Kim J.Y. Kang M.G. Kim S. Jo E.J. Kim M.H. Plevkova J. Park H.W. Cho S.H. Morice A.H. The global epidemiology of chronic cough in adults: A systematic review and meta-analysis. Eur. Respir. J. 2015 45 5 1479 1481 10.1183/09031936.00218714 25657027
    [Google Scholar]
  56. Ferrer R.A. Torregrossa M. Franz S. Germ-free, carefree: Injured skin uses IL-24 to kick-start repair independent of pathogen-recognition. Sig. Transduct. Target. Ther. 2023 8 379 10.1038/s41392‑023‑01609‑y
    [Google Scholar]
  57. Poindexter NJ Williams R Powis G Chada S Grimm EA. IL IL Expression of IL-24 and IL-24 receptors in human wound tissues and the biological implications of IL-24 on keratinocytes Wound Repair. Regen. 2012 20 6 896 903 10.1111/j.1524‑475X.2012.00840.x 23110359
    [Google Scholar]
  58. Smith S. Lopez S. Kim A. Kasteri J. Olumuyide E. Punu K. de la Parra C. Sauane M. Interleukin 24: Signal transduction pathways. Cancers 2023 15 13 3365 3365 10.3390/cancers15133365 37444474
    [Google Scholar]
  59. Chae WJ Bothwell ALM Canonical and non-canonical wnt signaling in immune cells. Trends Immunol 2018 39 10 830 847 10.1016/j.it.2018.08.006 30213499
    [Google Scholar]
  60. Song Q Xie Y Gou Q Guo X Yao Q Gou X. JAK/STAT3 and Smad3 activities are required for the wound healing properties of Periplaneta americana extracts. Int J Mol Med 2017 40 2 465 473 10.3892/ijmm.2017.3040. 28656220
    [Google Scholar]
  61. Donnelly R.P. Sheikh F. Kotenko S.V. Dickensheets H. The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J. Leukoc. Biol. 2004 76 2 314 321 10.1189/jlb.0204117 15123776
    [Google Scholar]
  62. Bosanquet D.C. Harding K.G. Ruge F. Sanders A.J. Jiang W.G. Expression of IL ‐24 and IL ‐24 receptors in human wound tissues and the biological implications of IL ‐24 on keratinocytes. Wound Repair Regen. 2012 20 6 896 903 10.1111/j.1524‑475X.2012.00840.x 23110359
    [Google Scholar]
  63. Mitamura Y. Nunomura S. Furue M. Izuhara K. IL-24: A new player in the pathogenesis of pro-inflammatory and allergic skin diseases. Allergol. Int. 2020 69 3 405 411 10.1016/j.alit.2019.12.003 31980374
    [Google Scholar]
  64. Qin K Yu M Fan J Wang H Zhao P Zhao G Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk. Genes Dis 2024 11 1 103 134 10.1016/j.gendis.2023.01.030 37588235
    [Google Scholar]
  65. Sun SC The non-canonical NF-κB pathway in immunity and inflammation. Nat Rev Immunol 2017 17 9 545 558 10.1038/nri.2017.52 28580957
    [Google Scholar]
  66. Tan Y. Sanders A.J. Zhang Y. Martin T.A. Owen S. Ruge F. Jiang W.G. Interleukin-24 (IL-24) expression and biological impact on HECV endothelial cells. Cancer Genomics Proteomics 2015 12 5 243 250 26417027
    [Google Scholar]
  67. Feng K. Cen J. Zou X. Zhang T. Novel insight into MDA-7/IL-24: A potent therapeutic target for autoimmune and inflammatory diseases. Clin. Immunol. 2024 266 110322 10.1016/j.clim.2024.110322 39033900
    [Google Scholar]
  68. Liu C. Zhang Q. Liu Z. Zhuang D. Wang S. Deng H. Shi Y. Sun J. Guo J. Wei F. Wu X. miR-21 expressed by dermal fibroblasts enhances skin wound healing through the regulation of inflammatory cytokine expression. Inflammation 2024 47 2 572 590 10.1007/s10753‑023‑01930‑2 38041730
    [Google Scholar]
  69. Ramey-Ward A.N. Walthall H.P. Smith S. Barrows T.H. Human keratin matrices promote wound healing by modulating skin cell expression of cytokines and growth factors. Wound Repair Regen. 2024 32 3 257 267 10.1111/wrr.13137 38111086
    [Google Scholar]
  70. Bordon Y. Hypoxia and IL-24 drive a sterile wound healing pathway. Nat Rev Immunol 2023 23 6 344 10.1038/s41577‑023‑00888‑4 37165170
    [Google Scholar]
  71. Liu S. Hur Y.H. Cai X. Cong Q. Yang Y. Xu C. Bilate A.M. Gonzales K.A.U. Parigi S.M. Cowley C.J. Hurwitz B. Luo J.D. Tseng T. Gur-Cohen S. Sribour M. Omelchenko T. Levorse J. Pasolli H.A. Thompson C.B. Mucida D. Fuchs E. A tissue injury sensing and repair pathway distinct from host pathogen defense. Cell 2023 186 10 2127 2143.e22 10.1016/j.cell.2023.03.031 37098344
    [Google Scholar]
  72. Zhong Y Zhang X Chong WP Interleukin-24 immunobiology and its roles in inflammatory diseases. Int J Mol Sci 2022 6 23 2 627 10.3390/ijms23020627 35054813
    [Google Scholar]
/content/journals/raiad/10.2174/0127722708349928250108191556
Loading
/content/journals/raiad/10.2174/0127722708349928250108191556
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: interleukin-24 (IL-24) ; angiogenesis ; Wound healing ; chronic wounds ; tissue repair
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