Chemerin 156F, generated by chymase cleavage of prochemerin, is elevated in joint fluids of arthritis patients. Arthritis research & therapy Zhao, L., Yamaguchi, Y., Ge, X., Robinson, W. H., Morser, J., Leung, L. L. 2018; 20 (1): 132


BACKGROUND: Chemerin is a chemoattractant involved in immunity that also functions as an adipokine. Chemerin is secreted as an inactive precursor (chem163S), and its activation requires proteolytic cleavages at its C-terminus, involving proteases in coagulation, fibrinolysis, and inflammation. Previously, we found chem158K was the dominant chemerin form in synovial fluids from patients with arthritis. In this study, we aimed to characterize a distinct cleaved chemerin form, chem156F, in osteoarthritis (OA) and rheumatoid arthritis (RA).METHODS: Purified chem156F was produced in transfected CHO cells. To quantify chem156F in OA and RA samples, we developed a specific ELISA for chem156F using antibody raised against a peptide representing the C-terminus of chem156F.RESULTS: Ca2+ mobilization assays showed that the EC50 values for chem163S, chem156F, and chem157S were 252±141nM, 133±41.5nM, and 5.83±2.48nM, respectively. chem156F was more active than its precursor, chem163S, but very much less potent than chem157S, the most active chemerin form. Chymase was shown to be capable of cleaving chem163S at a relevant rate. Using the chem156F ELISA we found a substantial amount of chem156F present in synovial fluids from patients with OA and RA, 24.06±5.51ng/ml and 20.35±5.19ng/ml (mean±SEM, n=25) respectively, representing 20% of total chemerin in OA and 76.7% of chemerin in RA synovial fluids.CONCLUSIONS: Our data show that chymase cleavage of chem163S to partially active chem156F can be found in synovial fluids where it can play a role in modulation of the inflammation in joints.

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