title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Ophthalmology, School of Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, People's Republic of China.|Shanghai Key Laboratory of Fundus Disease, No. 100, Haining Road, Shanghai, People's Republic of China.
authors.forename: Shaopin
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, School of Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, People's Republic of China.|Shanghai Key Laboratory of Fundus Disease, No. 100, Haining Road, Shanghai, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, School of Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, People's Republic of China.|Shanghai Key Laboratory of Fundus Disease, No. 100, Haining Road, Shanghai, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, School of Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, People's Republic of China.|Shanghai Key Laboratory of Fundus Disease, No. 100, Haining Road, Shanghai, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Ophthalmology, School of Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, People's Republic of China.|Shanghai Key Laboratory of Fundus Disease, No. 100, Haining Road, Shanghai, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Ophthalmology, School of Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, People's Republic of China.|Shanghai Key Laboratory of Fundus Disease, No. 100, Haining Road, Shanghai, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Ophthalmology, School of Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, People's Republic of China. drliukun@sjtu.edu.cn.|Shanghai Key Laboratory of Fundus Disease, No. 100, Haining Road, Shanghai, People's Republic of China. drliukun@sjtu.edu.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003315:Cornea / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007634:Keratitis / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D011070:Poly I-C; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; C581855:H-RN peptide; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010446:Peptide Fragments; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D017228:Hepatocyte Growth Factor; D020928:Mitogen-Activated Protein Kinases; D011070:Poly I-C
keywords: Corneal inflammation; Keratitis; LPS; Peptide; Poly(I:C)