Chemerin 156F, generated by chymase cleavage of prochemerin, is elevated in joint fluids of arthritis patients
| Autor: | John Morser, William H. Robinson, Xiaomei Ge, Lei Zhao, Yasuto Yamaguchi, Lawrence L.K. Leung |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteases medicine.medical_specialty lcsh:Diseases of the musculoskeletal system Arthritis Adipokine Enzyme-Linked Immunosorbent Assay Inflammation CHO Cells Arthritis Rheumatoid 03 medical and health sciences Chymases Cricetulus Cricetinae Internal medicine Synovial Fluid Osteoarthritis medicine Animals Humans Protein Isoforms Chemerin Protein Precursors biology Chemistry Chymase medicine.disease Recombinant Proteins 3. Good health Serine protease 030104 developmental biology Endocrinology Rheumatoid arthritis biology.protein Intercellular Signaling Peptides and Proteins Chemokines Antibody medicine.symptom lcsh:RC925-935 Research Article |
| Zdroj: | Arthritis Research & Therapy, Vol 20, Iss 1, Pp 1-9 (2018) Arthritis Research & Therapy |
| ISSN: | 1478-6362 |
| Popis: | 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 ± 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. Electronic supplementary material The online version of this article (10.1186/s13075-018-1615-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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