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Am J Physiol Lung Cell Mol Physiol 280: L1225-L1232, 2001;
1040-0605/01 $5.00
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Vol. 280, Issue 6, L1225-L1232, June 2001

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

Thomas Lahiri1, Johanne D. Laporte1, Paul E. Moore1, Reynold A. Panettieri Jr.2, and Stephanie A. Shore1

1 Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; and 2 Pulmonary and Critical Care Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Interleukin (IL)-1beta 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-1beta -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-1beta . In contrast, IL-6 and IL-11 did not alter IL-1beta -induced COX-2 expression. IL-6 did increase IL-1beta -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-1beta synergistically cause COX-2 expression and PGE2 release.

oncostatin; cyclooxygenase; prostaglandin; signal transducer and activator of transcription


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