Oncostatin M induces interleukin-6 and cyclooxygenase-2 expression in human vascular smooth muscle cells - Synergy with interleukin-1 beta

Oncostatin M (OSM), a cytokine first identified from activated monocytes an d T lymphocytes, is one of the most potent autocrine growth factor for AIDS and Kaposi's sarcoma. Little is known about the effects of OSM on normal v ascular cells. We thus exposed human aortic smooth muscle cells (hASMCs) to OSM, examined cell proliferation and morphology, and determined interleuki n-6 (IL-6) and cyclooxygenase-2 (COX-2) expression. OSM had a weak antiprol iferative effect. After a 4-day incubation with 100 ng/mL OSM, cell count d ecreased to 69+/-3% of control. However, OSM induced striking changes in hA SMC morphology, characterized by a polyclonal shape, in contrast to the spi ndle morphological feature of control hASMCs. OSM stimulated the release of IL-6 by hASMCs in a dose-dependent way; after a 48-hour exposure, values w ere 8.5+/-0.7, 29.7+/-3.5, 50.9+/-4.4, and 73.8+/-7.6X10(3) U/mL (n=6) at O SM concentrations of 0, 1, 10, and 100 ng/mL, respectively. OSM induced mar ked expression of COX-2 protein and mRNA. Leukemia inhibitory factor had no effect on hASMCs, indicating that OSM effects on hASMCs were mediated by t he OSM type II receptor and not by the leukemia inhibitory factor receptor. OSM used the JAK/STAT signaling pathway, as demonstrated by rapid phosphor ylation of JAK1 and specific activation of STAT1. Interestingly, OSM acted in synergy with IL-1 beta on IL-6 production and COX-2 expression. In concl usion, OSM is a novel regulator of human smooth muscle cell functions, acti ng in concert with IL-1 beta, and OSM may play a role in major vascular dis eases such as atherosclerosis.