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

Interleukin (IL)-1β induces cyclooxygenase (COX)-2 expression and prostanoid formation in cultured human airway smooth muscle (HASM) cells. In other cell types, IL-6 family cytokines induce COX-2 or augment IL-1β-induced COX-2 expression. The purpose of this study was to determine whether IL-6 family cytokines were involved in COX-2 expression in HASM cells. RT-PCR was used to demonstrate that the necessary receptor components for IL-6-type cytokine binding are expressed in HASM cells. IL-6 and oncostatin M (OSM) each caused a dose-dependent phosphorylation of signal transducer and activator of transcription-3, whereas IL-11 did not. IL-6, IL-11, and OSM alone had no effect on COX-2 expression. However, OSM caused dose-dependent augmentation of COX-2 expression and prostaglandin (PG) E₂ release induced by IL-1β. In contrast, IL-6 and IL-11 did not alter IL-1β-induced COX-2 expression. IL-6 did increase IL-1β-induced PGE₂ formation in unstimulated 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 release. Our results indicate that IL-6 and OSM are capable of inducing signaling in HASM cells. In addition, OSM and IL-1β synergistically cause COX-2 expression and PGE₂ release.