Source: International Congress 2014 – Cell biology 2014
Disease area: Airway diseases

Abstract

Background: Severe asthma is characterised by poor therapeutic response to corticosteroid (CS) therapy. We have previously demonstrated that airway smooth muscle (ASM) cells from severe asthma patients are more insensitive to CSs as demonstrated by its inhibition of TNFa-induced CCL11 release.Aims & Objectives: We determined whether this CS insensitivity is also observed with different stimuli using Poly(I:C) and TNFa, and with a wide range of cytokine/chemokine release panel. The response of ASM cells from severe asthmatics (n=15) was compared to those of non-severe asthmatics (n=7), idiopathic cough subjects (n=6) and healthy subjects (n=12).Methods: ASM cells were exposed to 10^-8 M fluticasone propionate (FP) for 2 hrs, prior to overnight stimulation with either 1 mg/ml Poly(I:C) or 1 ng/ml TNFa. Supernatants were collected for 32-Plex assay by Luminex and cells were harvested for RNA extraction and transcriptomic analysis.Results: At baseline, CX3CL1, CCL11, CXCL8, and IL-6 release was lower in severe asthmatic ASM cells compared to those of healthy subjects. Conversely, EGF and MIP-1b release was higher. Poly(I:C) and/or TNFa induced the release of most analytes tested. FP did not affect Poly(I:C)-induced CXCL10 or CXCL8 release, whereas Poly(I:C)-induced GM-CSF, IL-6 and MIP-1a was significantly reduced by FP in severe asthmatic ASM cells. TNFa-induced CXCL8, CXCL10 and CX3CL1 release was not affected by FP. On the contrary, FP had a significant effect on TNFa-induced IL-6 and GRO release.Conclusion: A differential corticosteroid signature has been identified in severe asthma, which is stimulus and analyte-dependent.

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Citations should be made in the following way:
C. Rossios, D. Gibeon, K. F. Chung, I. M. Adcock, U-BIOPRED study group (London, United Kingdom). Corticosteroid insensitivity in airway smooth muscle cells from severe asthma is dependent on stimulus and cytokine product. Eur Respir J 2014; 44: Suppl. 58, 3846

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