Effects of a novel peptide derived from human thrombomodulin on endotoxin-induced uveitis in vitro and in vivo |
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Authors: | Jin Huiyi Yang Xiaolu Liu Kun Gu Qing Xu Xun |
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Institution: | 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. |
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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. |
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