| Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases. | |
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MedLine Citation:
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PMID: 22268118 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 hr with the Th1 cytokines interleukin-1β (IL-1β) or tumour necrosis factor-α (TNFα), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNFα and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Non-asthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNFα or cytomix at 4-8 hr, with the highest levels detected in cytomix-stimulated asthmatic cells . Cell-associated syndecan-4 levels were decreased by 24 hr, whereas shedding remained elevated at 24 hr, consistent with newly synthesised syndecan-4 being shed. Inhibition of ASMC MMP-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. |
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Authors:
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Xiahui Tan; Najwa Khalil; Candice Tesarik; Karunasri Vanapalli; Viki Yaputra; Hatem Alkhouri; Brian G G Oliver; Carol L Armour; J Margaret Hughes |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-20 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: - ISSN: 1522-1504 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Woolcock Institute of Medical Research. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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