TGFβ1 induces IL-6 and inhibits IL-8 release in human bronchial epithelial cells: The role of Smad2/3
- Publication Type:
- Journal Article
- Citation:
- Journal of Cellular Physiology, 2010, 225 (3), pp. 846 - 854
- Issue Date:
- 2010-12-01
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2013005271OK.pdf | 1.17 MB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Ge, Q | en_US |
dc.contributor.author | Moir, LM | en_US |
dc.contributor.author | Black, JL | en_US |
dc.contributor.author |
Oliver, BG https://orcid.org/0000-0002-7122-9262 |
en_US |
dc.contributor.author | Burgess, JK | en_US |
dc.date.issued | 2010-12-01 | en_US |
dc.identifier.citation | Journal of Cellular Physiology, 2010, 225 (3), pp. 846 - 854 | en_US |
dc.identifier.issn | 0021-9541 | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/28540 | |
dc.description.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. © 2010 Wiley-Liss, Inc. | en_US |
dc.relation.ispartof | Journal of Cellular Physiology | en_US |
dc.relation.isbasedon | 10.1002/jcp.22295 | en_US |
dc.subject.classification | Biochemistry & Molecular Biology | en_US |
dc.subject.mesh | Bronchi | en_US |
dc.subject.mesh | Respiratory Mucosa | en_US |
dc.subject.mesh | Cells, Cultured | en_US |
dc.subject.mesh | Epithelial Cells | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Asthma | en_US |
dc.subject.mesh | JNK Mitogen-Activated Protein Kinases | en_US |
dc.subject.mesh | RNA, Messenger | en_US |
dc.subject.mesh | Inflammation Mediators | en_US |
dc.subject.mesh | Interleukin-8 | en_US |
dc.subject.mesh | Interleukin-6 | en_US |
dc.subject.mesh | Protein Kinase Inhibitors | en_US |
dc.subject.mesh | Blotting, Western | en_US |
dc.subject.mesh | Enzyme-Linked Immunosorbent Assay | en_US |
dc.subject.mesh | Case-Control Studies | en_US |
dc.subject.mesh | Chromatin Immunoprecipitation | en_US |
dc.subject.mesh | Polymerase Chain Reaction | en_US |
dc.subject.mesh | Signal Transduction | en_US |
dc.subject.mesh | Down-Regulation | en_US |
dc.subject.mesh | Up-Regulation | en_US |
dc.subject.mesh | Binding Sites | en_US |
dc.subject.mesh | Phosphorylation | en_US |
dc.subject.mesh | Adolescent | en_US |
dc.subject.mesh | Adult | en_US |
dc.subject.mesh | Aged | en_US |
dc.subject.mesh | Middle Aged | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Smad2 Protein | en_US |
dc.subject.mesh | Smad3 Protein | en_US |
dc.subject.mesh | Transforming Growth Factor beta1 | en_US |
dc.subject.mesh | Promoter Regions, Genetic | en_US |
dc.subject.mesh | Young Adult | en_US |
dc.title | TGFβ1 induces IL-6 and inhibits IL-8 release in human bronchial epithelial cells: The role of Smad2/3 | en_US |
dc.type | Journal Article | |
utslib.citation.volume | 3 | en_US |
utslib.citation.volume | 225 | en_US |
utslib.for | 1116 Medical Physiology | en_US |
utslib.for | 0601 Biochemistry and Cell Biology | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Strength - CHT - Health Technologies | |
utslib.copyright.status | closed_access | |
pubs.declined | 1970-01-01T00:00:00.0+1000 | |
pubs.issue | 3 | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 225 | en_US |
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. © 2010 Wiley-Liss, Inc.
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