Interleukin-6 family cytokines: signaling and effects in human airway smooth muscle cells

Interleukin (IL)-1 beta induces cyclooxygenase (COX)-2 expression and prost anoid formation in cultured human airway smooth muscle (HASM) cells. In oth er cell types, IL-6 family cytokines induce COX-2 or augment IL-1 beta -ind uced COX-2 expression. The purpose of this study was to determine whether I L-6 family cytokines were involved in COX-2 expression in HASM cells. RT-PC R was used to demonstrate that the necessary receptor components for IL-6-t ype cytokine binding are expressed in HASM cells. IL-6 and oncostatin M (OS M) each caused a dose-dependent phosphorylation of signal transducer and ac tivator of transcription-3, whereas IL-11 did not. IL-6, IL-11, and OSM alo ne had no effect on COX-2 expression. However, OSM caused dose-dependent au gmentation of COX-2 expression and prostaglandin (PG) E-2 release induced b y IL-1 beta. In contrast, IL-6 and IL-11 did not alter IL-1 beta -induced C OX-2 expression. IL-6 did increase IL-1 beta -induced PGE(2) formation in u nstimulated cells but not in cells stimulated with arachidonic acid (AA; 10 (-5) M), suggesting that IL-6 effects were mediated at the level of AA rele ase. Our results indicate that IL-6 and OSM are capable of inducing signali ng in HASM cells. In addition, OSM and IL-1 beta synergistically cause COX- 2 expression and PGE(2) release.