Oncostatin M causes eotaxin-1 release from airway smooth muscle: synergy with IL-4 and IL-13.
BACKGROUND: Eotaxin is implicated in asthmatic eosinophilia. Oncostatin M (OSM) causes eotaxin release from fibroblasts.
OBJECTIVE: We sought to examine the effects and mechanism of action of OSM and other IL-6 family cytokines on eotaxin release from human airway smooth muscle cells.
METHODS: Eotaxin 1 release was measured by means of ELISA. Western blotting was used to examine mitogen-activated protein kinase and signal transducer and activator of transcription 3 (STAT-3) phosphorylation. Eotaxin promoter activity was analyzed in cells transfected with wild-type STAT-3, a mutant form of STAT-3 that cannot be phosphorylated, and a constitutively active form of STAT-3. The mRNA and protein expression of IL-4R alpha, the signaling receptor for IL-4 and IL-13, was evaluated by means of real-time PCR and flow cytometry, respectively.
RESULTS: OSM increased eotaxin 1 release and augmented IL-4- or IL-13-induced eotaxin release, whereas other IL-6 family cytokines did not. OSM caused a greater increase in STAT-3 phosphorylation and STAT-3-mediated gene transcription than other IL-6 family cytokines. OSM increased eotaxin promoter activity and augmented IL-13- and IL-4-induced increases in promoter activity. The constitutively active form of STAT-3 increased eotaxin promoter activity, whereas the mutant form of STAT-3 that cannot be phosphorylated significantly reduced eotaxin promoter activity induced by OSM or IL-4 plus OSM. OSM increased IL-4R alpha mRNA and protein levels.
CONCLUSIONS: OSM induces eotaxin 1 expression in human airway smooth muscle cells by a mechanism involving STAT-3. OSM synergizes with IL-13 and IL-4 to increase eotaxin 1 expression, possibly as a result of effects on IL-4R alpha expression.
Published In/Presented At
Faffe, D. S., Flynt, L., Mellema, M., Moore, P. E., Silverman, E. S., Subramaniam, V., Jones, M. R., Mizgerd, J. P., Whitehead, T., Imrich, A., Panettieri, R. A., Jr, & Shore, S. A. (2005). Oncostatin M causes eotaxin-1 release from airway smooth muscle: synergy with IL-4 and IL-13. The Journal of allergy and clinical immunology, 115(3), 514–520. https://doi.org/10.1016/j.jaci.2004.11.033
Medicine and Health Sciences
Department of Medicine