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IL-20 promotes epithelial healing of the injured mouse cornea.
Exp Eye Res. 2017 01; 154:22-29.EE

Abstract

After corneal epithelial injury, the ensuing inflammatory response is necessary for efficient wound healing. While beneficial healing effects are attributed to recruited neutrophils and platelets, dysregulated inflammation (too little or too much) is associated with impaired wound healing. The purpose of this study was to use an established C57BL/6J mouse model of corneal injury to evaluate the potential modulatory role of interleukin-20 (IL-20) on the inflammatory and healing responses to epithelial wounding. In the uninjured cornea, immunofluorescence staining for IL-20 and its receptor, IL-20RA, was observed on basal epithelial cells at the limbus. After a 2 mm central epithelial abrasion, IL-20 staining was also observed in stromal keratocytes and ELISA studies showed a significant increase (nearly 3-fold) in IL-20 expression. Injured corneas healed more slowly when treated with a topical application of a neutralizing anti-IL-20 antibody. While corneal epithelial cell division and epithelial nerve recovery measured at 24 h post-injury were reduced compared to controls, neutrophil influx into the cornea was increased. In contrast, topical application of recombinant IL-20 (rIL-20) decreased corneal inflammation as evidenced by reductions in limbal vessel dilatation, platelet extravasation, neutrophil recruitment and CXCL1 expression. In wild type mice, topical rIL-20 had a limited effect on corneal wound healing and resulted in only a slight increase in epithelial cell division and epithelial nerve recovery; the rate of wound closure was unaffected. To clarify the effect of IL-20 on corneal wound healing, rIL-20 was topically applied to neutropenic wild type (WT) mice and mutant mice (ɣδ T cell deficient mice and CD11a deficient mice), all of which have well characterized reductions in neutrophil recruitment and delayed wound healing after corneal injury. In each case, rIL-20 restored corneal wound healing to baseline levels while neutrophil recruitment remained low. Thus, it appears that IL-20 plays a beneficial and direct role in corneal wound healing while negatively regulating neutrophil and platelet infiltration.

Authors+Show Affiliations

College of Optometry, University of Houston, United States.College of Optometry, University of Houston, United States.Department of Pediatrics, Baylor College of Medicine, United States; International Collaborative Innovation Research Center of Ocular Surface Diseases and Institute of Ophthalmology, Jinan University School of Medicine, Guangzhou, China.Department of Pediatrics, Baylor College of Medicine, United States.College of Optometry, University of Houston, United States; Department of Pediatrics, Baylor College of Medicine, United States. Electronic address: aburns@central.uh.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27818315

Citation

Zhang, Wanyu, et al. "IL-20 Promotes Epithelial Healing of the Injured Mouse Cornea." Experimental Eye Research, vol. 154, 2017, pp. 22-29.
Zhang W, Magadi S, Li Z, et al. IL-20 promotes epithelial healing of the injured mouse cornea. Exp Eye Res. 2017;154:22-29.
Zhang, W., Magadi, S., Li, Z., Smith, C. W., & Burns, A. R. (2017). IL-20 promotes epithelial healing of the injured mouse cornea. Experimental Eye Research, 154, 22-29. https://doi.org/10.1016/j.exer.2016.11.006
Zhang W, et al. IL-20 Promotes Epithelial Healing of the Injured Mouse Cornea. Exp Eye Res. 2017;154:22-29. PubMed PMID: 27818315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-20 promotes epithelial healing of the injured mouse cornea. AU - Zhang,Wanyu, AU - Magadi,Sri, AU - Li,Zhijie, AU - Smith,C Wayne, AU - Burns,Alan R, Y1 - 2016/11/03/ PY - 2016/08/11/received PY - 2016/10/06/revised PY - 2016/11/02/accepted PY - 2016/11/8/pubmed PY - 2017/6/16/medline PY - 2016/11/8/entrez KW - Cornea KW - Healing KW - Inflammation KW - Injury KW - Interleukin-20 SP - 22 EP - 29 JF - Experimental eye research JO - Exp Eye Res VL - 154 N2 - After corneal epithelial injury, the ensuing inflammatory response is necessary for efficient wound healing. While beneficial healing effects are attributed to recruited neutrophils and platelets, dysregulated inflammation (too little or too much) is associated with impaired wound healing. The purpose of this study was to use an established C57BL/6J mouse model of corneal injury to evaluate the potential modulatory role of interleukin-20 (IL-20) on the inflammatory and healing responses to epithelial wounding. In the uninjured cornea, immunofluorescence staining for IL-20 and its receptor, IL-20RA, was observed on basal epithelial cells at the limbus. After a 2 mm central epithelial abrasion, IL-20 staining was also observed in stromal keratocytes and ELISA studies showed a significant increase (nearly 3-fold) in IL-20 expression. Injured corneas healed more slowly when treated with a topical application of a neutralizing anti-IL-20 antibody. While corneal epithelial cell division and epithelial nerve recovery measured at 24 h post-injury were reduced compared to controls, neutrophil influx into the cornea was increased. In contrast, topical application of recombinant IL-20 (rIL-20) decreased corneal inflammation as evidenced by reductions in limbal vessel dilatation, platelet extravasation, neutrophil recruitment and CXCL1 expression. In wild type mice, topical rIL-20 had a limited effect on corneal wound healing and resulted in only a slight increase in epithelial cell division and epithelial nerve recovery; the rate of wound closure was unaffected. To clarify the effect of IL-20 on corneal wound healing, rIL-20 was topically applied to neutropenic wild type (WT) mice and mutant mice (ɣδ T cell deficient mice and CD11a deficient mice), all of which have well characterized reductions in neutrophil recruitment and delayed wound healing after corneal injury. In each case, rIL-20 restored corneal wound healing to baseline levels while neutrophil recruitment remained low. Thus, it appears that IL-20 plays a beneficial and direct role in corneal wound healing while negatively regulating neutrophil and platelet infiltration. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/27818315/IL_20_promotes_epithelial_healing_of_the_injured_mouse_cornea_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(16)30417-1 DB - PRIME DP - Unbound Medicine ER -