Interleukin-6 family cytokines: signaling and effects in human airway smooth muscle cells.
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) E(2) 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 PGE(2) 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 PGE(2) release.
Lahiri
T
T
Physiology Program, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA.
Laporte
J D
JD
Moore
P E
PE
Panettieri
R A
RA
Shore
S A
SA
D015703:Antigens, CD / Q000096:biosynthesis; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D017370:Interleukin-11 / Q000494:pharmacology; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053702:Receptors, Interleukin-11; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis; D053677:Receptors, Oncostatin M; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014132:Trachea; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C508428:IL11RA protein, human; C494199:IL6ST protein, human; D007375:Interleukin-1; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C508351:OSM protein, human; D010455:Peptides; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D019947:Receptors, Interleukin-6; D053677:Receptors, Oncostatin M; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020929:Mitogen-Activated Protein Kinase Kinases; D015232:Dinoprostone