CONSTITUTIVE mRNA AND PROTEIN PRODUCTION OF MACROPHAGE COLONY-STIMULATING FACTOR BUT NOT OF OTHER CYTOKINES BY SYNOVIAL FIBROBLASTS FROM RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS PATIENTS

This study analyses the mRNA and protein production and their regulation of macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8 and IL-6 by synovial fibroblasts obtained from patients with RA and OA. M-CSF was found to be produced constitutively as opposed to other cytokines. Stimulation of the cells with IL-1β caused a marked increase of GM-CSF, IL-8, IL-6 and as well as of M-CSF mRNA levels. In parallel, a time-dependent increase of M-CSF, GM-CSF, IL-8 and IL-6 protein production was observed. Among the cytokine mRNAs examined only that of M-CSF exhibited a pronounced stability in unstimulated synovial fibroblasts, whereas the other cytokines displayed short mRNA half-lives of 1-2 h. Induction by IL-1β markedly prolonged IL-8, IL-6 and GM-CSF mRNA half-lives to >8 h which indicates increased mRNA stability. These findings suggest that among the cytokines that are produced in the inflamed synovium M-CSF may be particularly important for sustaining long-term influx, activation and survival of mononuclear phagocytes. GM-CSF, IL-8 and IL-6, by contrast, may be more involved in more acute cellular response