Chemerin 156F, generated by chymase cleavage of prochemerin, is elevated in joint fluids of arthritis patients
Year: 2018
Type: article
Abstract: 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: values for chem163S, chem156F, and chem157S were 252 ± 141 nM, 133 ± 41.5 nM, and 5.83 ± 2.48 nM, 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 ± 5.51 ng/ml and 20.35 ± 5.19 ng/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.
Source: Arthritis Research & Therapy
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,690
Funders: U.S. Department of Veterans Affairs, National Institutes of Health, Office of Academic Affiliations, Department of Veterans Affairs, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1202804413, G1798808941, G2093165041, G226215853, G2641536167, G2706824255, G3756351754, G3856546493, Cross-talk Between Coagulation, Inflammation, and Immunity, Large-Scale Characterization of Autoantibody Responses in Rheumatoid Arthritis, G5090192612, G5142113920, G5855316245, G6903504540, G7978527885, ACE: Autoimmunity Center of Excellence (ACE) at Stanford
OpenAlex ID: W2811016502