However, in the present study both cultured chondrocytes and cells in native tissue were immuno positive towards chemerin. Taken together with the finding that also mRNA for prochemerin was present in chondrocytes, this strongly suggests that these cells produce prochemerin that may serve as substrate for neutrophil derived serine proteases to generate che merin21 157. Hence, resident chondrocytes secrete a chemokine precursor that, after enzymatic cleavage by enzymes secreted by neutrophils, further may recruit leukocytes expressing the ChemR23 receptor. In addi tion, the cleavage product chemerin21 157 can bind the ChemR23 receptor expressed by chondrocytes which promote their secretion of pro inflammatory cytokines and MMPs.
A marked elevation of IL 8 and IL 6 was observed as a result of chemerin21 157 stimulation, whereas TNF a and IL 1b were modestly altered. you can check here “” Nevertheless, despite low levels these may be sufficient to orchestrate an inflammatory process due to their strong synergistic effects, even at low concentrations. In contrast, there is a rather indisputably strong association between the content of TNF a in synovial fluid and disease activ ity such as in rheumatoid arthritis. In our study, the sole cytokine source was the chondrocytes, unlike the situation occurring in a diseased joint where leukocytes are also present. Yet according to previous reports, the production of IL 6, IL 8 and MMPs in chondrocytes is assigned to the action of TNF a and IL 1b.
However, chemerin21 157 may have induced an immedi ate release of TNF a and IL 1b followed by internaliza tion and degradation, whereas IL 6, IL 8 and MMPs rely on the autocrine action of TNF a and IL 1b as reflected at the time of measurement. IL 8 exerts a potent chemotactic activity towards neu trophils, whereby it selleck chemical has a decisive role in the initial stages of inflammation. Even so, the present study indi cates that chemerin may be a prerequisite for an aug mented secretion of IL 8. Consequently, chemerin ChemR23 could serve as a central link for the initiation and maintenance of inflammation in joints. It has previously been described that chondrocytes produce IL 6 in response to physiologic and inflamma tory stimuli, and that IL 6 may serve as a mediator coordinating responses to cartilage injury.
Since IL 6 modulates the growth and differentiation of B and T lymphocytes, our findings propose that chemerinChemR23 signalling may contribute to the activation of B and T cells leading to engagement of adaptive immunity and further maturation of inflamma tion in joints. MMP 2, MMP 3 and MMP 13 cleave the most abun dant proteoglycan in cartilage, aggrecan, at the Asn373 Phe342 bond, and the resulting major fragment can be detected in the synovial fluid from patients with various arthritic diseases.