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TGFβ1 induces IL-6 and inhibits IL-8 release in human bronchial epithelial cells: The role of Smad2/3.
- Source :
-
Journal of Cellular Physiology . Nov2010, Vol. 225 Issue 3, p846-854. 9p. 1 Chart, 6 Graphs. - Publication Year :
- 2010
-
Abstract
- Human bronchial epithelial (HBE) cells contribute to asthmatic airway inflammation by secreting cytokines, chemokines, and growth factors, including interleukin (IL)-6, IL-8 and transforming growth factor (TGF) β1, all of which are elevated in asthmatic airways. This study examines the signaling pathways leading to TGFβ1 induced IL-6 and IL-8 in primary HBE cells from asthmatic and non-asthmatic volunteers. HBE cells were stimulated with TGFβ1 in the presence or absence of signaling inhibitors. IL-6 and IL-8 protein and mRNA were measured by ELISA and real-time PCR respectively, and cell signaling kinases by Western blot. TGFβ1 increased IL-6, but inhibited IL-8 production in both asthmatic and non-asthmatic cells; however, TGF induced significantly more IL-6 in asthmatic cells. Inhibition of JNK MAP kinase partially reduced TGFβ1 induced IL-6 in both cell groups. TGFβ1 induced Smad2 phosphorylation, and blockade of Smad2/3 prevented both the TGFβ1 modulated IL-6 increase and the decrease in IL-8 production in asthmatic and non-asthmatic cells. Inhibition of Smad2/3 also increased basal IL-8 release in asthmatic cells but not in non-asthmatic cells. Using CHIP assays we demonstrated that activated Smad2 bound to the IL-6, but not the IL-8 promoter region. We conclude that the Smad2/3 pathway is the predominant TGFβ1 signaling pathway in HBE cells, and this is altered in asthmatic bronchial epithelial cells. Understanding the mechanism of aberrant pro-inflammatory cytokine production in asthmatic airways will allow the development of alternative ways to control airway inflammation. J. Cell. Physiol. 225: 846-854, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219541
- Volume :
- 225
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Cellular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 53559665
- Full Text :
- https://doi.org/10.1002/jcp.22295