|TGFβ1 induces IL-6 and inhibits IL-8 release in human bronchial epithelial cells: the role of Smad2/3.|
|PMID: 20607798 Owner: NLM Status: MEDLINE|
|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.|
|Qi Ge; Lyn M Moir; Judith L Black; Brian G Oliver; Janette K Burgess|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: Journal of cellular physiology Volume: 225 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 Nov|
|Created Date: 2010-09-15 Completed Date: 2010-10-12 Revised Date: -|
Medline Journal Info:
|Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States|
|Languages: eng Pagination: 846-54 Citation Subset: IM|
|© 2010 Wiley-Liss, Inc.|
|Respiratory Research Group, Discipline of Pharmacology, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia. email@example.com|
|APA/MLA Format Download EndNote Download BibTex|
Asthma / immunology*, metabolism
Bronchi / drug effects, immunology*, metabolism
Enzyme-Linked Immunosorbent Assay
Epithelial Cells / drug effects, immunology*, metabolism
Inflammation Mediators / metabolism*
Interleukin-6 / genetics, metabolism*
Interleukin-8 / genetics, metabolism*
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism
Polymerase Chain Reaction
Promoter Regions, Genetic
Protein Kinase Inhibitors / pharmacology
RNA, Messenger / metabolism
Respiratory Mucosa / drug effects, immunology*, metabolism
Smad2 Protein / antagonists & inhibitors, metabolism*
Smad3 Protein / antagonists & inhibitors, metabolism*
Transforming Growth Factor beta1 / metabolism*
|0/IL6 protein, human; 0/IL8 protein, human; 0/Inflammation Mediators; 0/Interleukin-6; 0/Interleukin-8; 0/Protein Kinase Inhibitors; 0/RNA, Messenger; 0/SMAD2 protein, human; 0/SMAD3 protein, human; 0/Smad2 Protein; 0/Smad3 Protein; 0/Transforming Growth Factor beta1; EC 188.8.131.52/JNK Mitogen-Activated Protein Kinases|
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