Document Detail


TGFβ1 induces IL-6 and inhibits IL-8 release in human bronchial epithelial cells: the role of Smad2/3.
MedLine Citation:
PMID:  20607798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Qi Ge; Lyn M Moir; Judith L Black; Brian G Oliver; Janette K Burgess
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  225     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2010 Nov 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  846-54     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc.
Affiliation:
Respiratory Research Group, Discipline of Pharmacology, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia. qi.ge@sydney.edu.au
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Asthma / immunology*,  metabolism
Binding Sites
Blotting, Western
Bronchi / drug effects,  immunology*,  metabolism
Case-Control Studies
Cells, Cultured
Chromatin Immunoprecipitation
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Epithelial Cells / drug effects,  immunology*,  metabolism
Female
Humans
Inflammation Mediators / metabolism*
Interleukin-6 / genetics,  metabolism*
Interleukin-8 / genetics,  metabolism*
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Male
Middle Aged
Phosphorylation
Polymerase Chain Reaction
Promoter Regions, Genetic
Protein Kinase Inhibitors / pharmacology
RNA, Messenger / metabolism
Respiratory Mucosa / drug effects,  immunology*,  metabolism
Signal Transduction
Smad2 Protein / antagonists & inhibitors,  metabolism*
Smad3 Protein / antagonists & inhibitors,  metabolism*
Transforming Growth Factor beta1 / metabolism*
Up-Regulation
Young Adult
Chemical
Reg. No./Substance:
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 2.7.11.24/JNK Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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