Journal
EXPERIMENTAL CELL RESEARCH
Volume 315, Issue 20, Pages 3486-3499Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2009.09.024
Keywords
Oncostatin M; IL-4R alpha; IL-13R alpha 1; Eotaxin-1; Fibroblasts
Categories
Funding
- Canadian Institutes of Health Research (CIHR)
Ask authors/readers for more resources
Oncostatin M (OSM), a pleiotropic cytokine and a member of the gp130/IL-6 cytokine family, has been implicated in regulation of various chronic inflammatory processes. Previous work has shown that OSM induces eosinophil accumulation in mouse lungs in vivo and stimulates the eosinophil-selective chemokine eotaxin-1 synergistically with IL-4 in vitro. To examine the role of receptor regulation by OSM in synergistic eotaxin-1 responses, we here examine the modulation of the type-II IL-4 receptor (IL-4R alpha and IL-13R alpha 1) by OSM and other gp130/IL-6 cytokine family members using NIH3T3 fibroblasts and primary mouse lung fibroblasts. We first show that OSM with either IL-13 or IL-4 synergistically induces eotaxin-1 expression in a dose-dependent fashion. Analysis of IL-4R alpha expression at the protein (Western blot and FACS) and RNA (TAQMAN) levels showed that OSM markedly elevates expression by 3 h. OSM enhanced IL-13R alpha 1 mRNA and induced a smaller but detectable increase in total IL-13R alpha 1 protein. Priming fibroblasts with OSM for 6 h markedly enhanced subsequent IL-13 and IL-4-induced eotaxin-1 responses and STAT6 tyrosine-641 phosphorylation. Regulation of IL-4R alpha by OSM was sensitive to inhibition of the P13' K pathway by LY294002. These studies provide novel mechanistic insights in OSM role in regulation of synergistic eotaxin-1 responses and IL-4R alpha expression in fibroblasts. (C) 2009 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available