ONCOSTATIN-M INHIBITS IL-1-INDUCED EXPRESSION OF IL-8 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR BY SYNOVIAL AND LUNG FIBROBLASTS

The role of oncostatin M (OM) in modulating production of cytokines by connective tissue cells is largely unexplored, We have examined the e ffects of stimulating fibroblast cultures derived from human synovium and from normal lung with OM alone or in combination with IL-1, IL-1 a lpha (or IL-1 beta) at 1 or 5 ng/ml, stimulated production of high lev els of granulocyte-macrophage CSF (GM-CSF), IL-8, and IL-6 protein, At various concentrations (0.1-50 ng/ml), OM alone failed to significant ly enhance protein or mRNA levels of CM-CSF, IL-8, IL-6, or G-CSF afte r 18 h of stimulation. When combined with IL-1 alpha or -beta, OM caus ed a dose-dependent inhibition of the IL-1-induced level of IL-8 and G M-CSF protein and mRNA expression, whereas IL-6 production was simulta neously enhanced, In contrast, when IL-6 or leukemia inhibitory factor (two other cytokines that share gp130 receptor components with OM) we re used in a similar fashion in combination with IL-1 alpha, neither c ytokine consistently altered the IL-1-induced levels of IL-8, GM-CSF, or IL-6, In addition, only OM and not IL-6 or leukemia inhibitory fact or was able to induce STAT-1 nuclear factor binding to DNA in stimulat ed fibroblast extracts as measured by electrophoretic mobility shift a ssay, These results suggest that OM can significantly alter cytokine p rofiles of stimulated fibroblasts and may play a unique role in modula ting cytokine production by these cells at sites of inflammation.