Inhibitory effect of a novel peptide, H-RN, on keratitis induced by LPS or poly(I:C) in vitro and in vivo via suppressing NF-κB and MAPK activation. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Zhu, Shaopin; Xu, Xun; Wang, Lili; Su, Li; Gu, Qing; Wei, Fang; Liu, Kun
• Is Part Of: Journal of translational medicine. Volume 15:Issue 1(2017)
• Page Start: 1
• Page End: 14
• Publication Date: 2017-12
• Subjects: Keratitis -- Corneal inflammation -- Peptide -- LPS -- Poly(I:C); Medicine, Experimental -- Periodicals; Human experimentation in medicine -- Periodicals; Therapeutics -- Periodicals; 615.50724
• DOI: 10.1186/s12967-017-1121-z
• Languages: English
• ISSNs: 1479-5876

Abstract

Abstract Background Keratitis is a common cause of blindness. Current anti-inflammatory drugs used in keratitis have profound side effects. Small peptides derived from endogenous proteins potentially display both desired efficiency and safety. We identified an 11-amino-acid peptide, H-RN, from hepatocyte growth factor (HGF), an endogenous protein with anti-inflammatory properties. We evaluated the effects of H-RN in keratitis in vitro and in vivo. Methods In vitro, corneal fibroblasts were stimulated with LPS or poly(I:C), surrogates for bacteria and viruses. Inflammatory cytokines, intercellular cell adhesion molecule-1 (ICAM-1), translocation of NF-κB p65, activation of IκBα, NF-κB, and MAPKs were detected. In vivo, keratitis in rats was induced by LPS. Clinical, histological observation, and quantification of cytokines in the cornea were conducted. H-RN safety was measured by cell viability, clinical, histological, and microstructural observations. Results H-RN inhibited IL-6, monocyte chemotactic protein-1(MCP-1), Interferon- γ(IFN-γ), and ICAM-1 expression triggered by LPS or poly(I:C), alleviated the clinical manifestation and reduced the clinical score in keratitis in vivo. The histological disorder and proinflammatory cytokines of the cornea were also reduced. The translocation of NF-κB and phosphorylation of IκBα, NF-κB, p38, JNK, and ERK were significantly inhibited by H-RN. No sign of toxicity was observed. Conclusions H-RN effectively attenuated keratitis in vivo and in vitro induced by LPS or poly(I:C) through blocking NF-κB and MAPK signaling pathways. It may be a promising and safe agent in treating keratitis.