title: Effects of a novel peptide derived from human thrombomodulin on endotoxin-induced uveitis in vitro and in vivo.
abstract: Thrombomodulin (TM) is a single-transmembrane glycoprotein receptor for thrombin, which is best known as a cofactor for thrombin-mediated activation of anticoagulant protein C. C-type lectin-like domain (CTLD) of TM has distinct coagulation/fibrinolysis-independent anti-inflammatory properties. Here we found anti-inflammatory effects of a novel peptide (GC31) from CTLD of TM in endotoxin-induced uveitis, which was characterized by a reduction of leukocyte counts, protein concentration, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 levels in aqueous humor. Through in vitro experiments, we further found that GC31 suppressed TNF-α and interleukin (IL)-6 expressions in lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells and interrupted LPS-induced nuclear factor-κB (NF-κB) activation. These data indicate a beneficial role of peptide GC31 in preventing intraocular inflammatory response, especially uveitis.
authors: Shanghai Key Laboratory of Ocular Fundus Diseases, Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiaotong University, No. 100 Haining Road, Shanghai 200080, PR China.
authors: Huiyi
authors: H
authors: Jin
authors: Xiaolu
authors: X
authors: Yang
authors: Kun
authors: K
authors: Liu
authors: Qing
authors: Q
authors: Gu
authors: Xun
authors: X
authors: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D017208:Rats, Wistar; D018180:Thrombomodulin / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010446:Peptide Fragments; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha