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

Huiyi Jin; Xiaolu Yang; Kun Liu; Qing Gu; Xun Xu

doi:10.1016/j.febslet.2011.10.002

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

FEBS Lett. 2011 Nov 4;585(21):3457-64. doi: 10.1016/j.febslet.2011.10.002. Epub 2011 Oct 10.

Authors

Huiyi Jin¹, Xiaolu Yang, Kun Liu, Qing Gu, Xun Xu

Affiliation

¹ 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.

PMID: 22001200
DOI: 10.1016/j.febslet.2011.10.002

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / metabolism
Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use
Aqueous Humor / drug effects
Aqueous Humor / metabolism
Cell Line
Chemokine CCL2 / metabolism
Endotoxins / toxicity*
Gene Expression Regulation / drug effects
Humans
Interleukin-6 / genetics
Lipopolysaccharides / pharmacology
Macrophages / drug effects
Macrophages / metabolism
Male
Mice
Molecular Sequence Data
NF-kappa B / metabolism
Peptide Fragments / chemistry
Peptide Fragments / metabolism
Peptide Fragments / pharmacology*
Peptide Fragments / therapeutic use
Protein Structure, Tertiary
Protein Transport / drug effects
Rats, Wistar
Thrombomodulin / chemistry*
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism
Uveitis / chemically induced*
Uveitis / drug therapy*
Uveitis / metabolism
Uveitis / pathology

Substances

Anti-Inflammatory Agents
Ccl2 protein, mouse
Chemokine CCL2
Endotoxins
Interleukin-6
Lipopolysaccharides
NF-kappa B
Peptide Fragments
Thrombomodulin
Tumor Necrosis Factor-alpha