Effects of a novel peptide derived from human thrombomodulin on endotoxin-induced uveitis in vitro and in vivo

► We found a novel anti-inflammatory peptide (GC31) from human thrombomodulin. ► GC31 peptide suppressed the development of endotoxin induced uveitis. ► GC31 decreased leukocyte counts and protein concentration in aqueous humor. ► GC31 inhibited LPS-induced TNF-α, IL-6 and MCP-1 expression in vivo and in vitro. ► GC31 interrupted LPS-induced NF-κB activation in vitro. 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.