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Vol. 160, No. 1, 2013
Issue release date: December 2012
Section title: Original Paper
Int Arch Allergy Immunol 2013;160:75–85
(DOI:10.1159/000339697)

Secreted Factors from Human Mast Cells Trigger Inflammatory Cytokine Production by Human Airway Smooth Muscle Cells

Xia Y.C. · Harris T. · Stewart A.G. · Mackay G.A.
Department of Pharmacology, University of Melbourne, Parkville, Vic., Australia

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 2/13/2012 10:55:22 AM
Accepted: 5/21/2012
Published online: 9/1/2012
Issue release date: December 2012

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA

Abstract

Background: A notable feature of allergic asthma is the infiltration of mast cells into smooth muscle in the human airway. Thus, mast cells and human airway smooth muscle (hASM) cells are likely to exhibit mutual functional modulation via direct cell-cell contact or through released factors. This study examined mast cell modulation of hASM cell cytokine release. Methods: The mast cell line HMCα was used to model mast cell function. hASM cells were either co-cultured directly with resting or IgE/antigen-stimulated HMCα cells or treated with HMCα-conditioned media to examine the impact on cytokine release. The activation pathways triggered in hASM cells by the mast cell-derived factors were examined through the use of selective inhibitors and by Western blotting. Results: HMCα cells, or their conditioned media, induced the expression of cytokines (IL-8 and IL-6) by hASM cells at both the mRNA and the protein level. Cytokine expression in hASM cells was greatly amplified when HMCα cells were IgE/antigen-activated. The effects of the conditioned media were not mediated by the chemokines MCP-1 and MIP-1α or by exosomes. While the mast cell-derived factor(s) increased p38MAPK phosphorylation in hASM cells, cytokine production was not inhibited by the p38MAPK inhibitor SB203580. hASM cell production of IL-8 induced by HMCα condition media but not IL-6 was, however, attenuated by the Src tyrosine kinase inhibitor PP2. Conclusions: Our study shows that the release of soluble mediators by activated mast cells can stimulate hASM cells to elicit production of proinflammatory cytokines that may then exacerbate airway inflammation in asthma.

© 2012 S. Karger AG, Basel


  

Author Contacts

Correspondence to: Dr. Graham A. Mackay
Department of Pharmacology, University of Melbourne
Medical Building, Grattan Street
Parkville, VIC 3010 (Australia)
Tel. +61 3 8344 3932, E-Mail gmackay@unimelb.edu.au

  

Article Information

Received: February 13, 2012
Accepted after revision: May 21, 2012
Published online: September 1, 2012
Number of Print Pages : 11
Number of Figures : 4, Number of Tables : 0, Number of References : 62
Additional supplementary material is available online - Number of Parts : 2

  

Publication Details

International Archives of Allergy and Immunology

Vol. 160, No. 1, Year 2013 (Cover Date: December 2012)

Journal Editor: Valenta R. (Vienna)
ISSN: 1018-2438 (Print), eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 2/13/2012 10:55:22 AM
Accepted: 5/21/2012
Published online: 9/1/2012
Issue release date: December 2012

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: http://www.karger.com/IAA


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