Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases

Tan, X; Khalil, N; Tesarik, C; Vanapalli, K; Yaputra, V; Alkhouri, H; Oliver, BGG; Armour, CL; Margaret Hughes, J

Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases

Tan, X Khalil, N Tesarik, C Vanapalli, K Yaputra, V Alkhouri, H Oliver, BGG

Armour, CL Margaret Hughes, J

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Publication Type:: Journal Article
Citation:: American Journal of Physiology - Lung Cellular and Molecular Physiology, 2012, 302 (7)
Issue Date:: 2012-04-01

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Field	Value	Language
dc.contributor.author	Tan, X	en_US
dc.contributor.author	Khalil, N	en_US
dc.contributor.author	Tesarik, C	en_US
dc.contributor.author	Vanapalli, K	en_US
dc.contributor.author	Yaputra, V	en_US
dc.contributor.author	Alkhouri, H	en_US
dc.contributor.author	Oliver, BGG https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Armour, CL	en_US
dc.contributor.author	Margaret Hughes, J	en_US
dc.date.issued	2012-04-01	en_US
dc.identifier.citation	American Journal of Physiology - Lung Cellular and Molecular Physiology, 2012, 302 (7)	en_US
dc.identifier.issn	1040-0605	en_US
dc.identifier.uri	http://hdl.handle.net/10453/28533
dc.description.abstract	In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan- 4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma. © 2012 the American Physiological Society.	en_US
dc.relation.ispartof	American Journal of Physiology - Lung Cellular and Molecular Physiology	en_US
dc.relation.isbasedon	10.1152/ajplung.00167.2011	en_US
dc.subject.classification	Respiratory System	en_US
dc.subject.mesh	Muscle, Smooth	en_US
dc.subject.mesh	Lung	en_US
dc.subject.mesh	Th1 Cells	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Myocytes, Smooth Muscle	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	Extracellular Signal-Regulated MAP Kinases	en_US
dc.subject.mesh	JNK Mitogen-Activated Protein Kinases	en_US
dc.subject.mesh	Tumor Necrosis Factor-alpha	en_US
dc.subject.mesh	RNA, Messenger	en_US
dc.subject.mesh	MAP Kinase Signaling System	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	Matrix Metalloproteinase 2	en_US
dc.subject.mesh	Interleukin-1beta	en_US
dc.subject.mesh	Syndecan-4	en_US
dc.subject.mesh	Interferon-gamma	en_US
dc.subject.mesh	Young Adult	en_US
dc.subject.mesh	Airway Remodeling	en_US
dc.subject.mesh	Matrix Metalloproteinase Inhibitors	en_US
dc.title	Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.citation.volume	302	en_US
utslib.for	1116 Medical Physiology	en_US
utslib.for	0606 Physiology	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.issue	7	en_US
pubs.publication-status	Published	en_US
pubs.volume	302	en_US

Abstract:

In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan- 4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma. © 2012 the American Physiological Society.

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http://hdl.handle.net/10453/28533