IL-17A Mediates a Selective Gene Expression Profile in Asthmatic Human Airway Smooth Muscle Cells

被引:20
作者
Dragon, Stephane [1 ]
Hirst, Stuart J. [2 ]
Lee, Tak H. [3 ,4 ]
Gounni, Abdelilah S. [1 ]
机构
[1] Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 0T5, Canada
[2] Monash Univ, Dept Physiol, Melbourne, Vic 3168, Australia
[3] Kings Coll London, MRC, Div Asthma Allergy & Lung Biol, London, England
[4] Asthma United Kingdom Ctr Allerg Mech Asthma, London, England
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
IL-17RA; signal transduction; gene expression; airway smooth muscle cells; NF-KAPPA-B; MESSENGER-RNA; T-CELLS; NEGATIVE FEEDBACK; ACTIVATION; CHEMOKINE; RECEPTOR; FAMILY; TRANSCRIPTION; LYMPHOCYTES;
D O I
10.1165/rcmb.2012-0267OC
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Airway smooth muscle (ASM) cells are thought to contribute to the pathogenesis of allergic asthma by orchestrating and perpetuating airway inflammation and remodeling responses. In this study, we evaluated the IL-17RA signal transduction and gene expression profile in ASM cells from subjects with mild asthma and healthy individuals. Human primary ASM cells were treated with IL-17A and probed by the Affymetrix GeneChip array, and gene targets were validated by real-time quantitative RT-PCR. Genomic analysis underlined the proinflammatory nature of IL-17A, as multiple NF-kappa B regulatory factors and chemokines were induced in ASM cells. Transcriptional regulators consisting of primary response genes were overrepresented and displayed dynamic expression profiles. IL-17A poorly enhanced IL-1 beta or IL-22 gene responses in ASM cells from both subjects with mild asthma and healthy donors. Interestingly, protein modifications to the NF-kappa B regulatory network were not observed after IL-17A stimulation, although oscillations in I kappa B epsilon expression were detected. ASM cells from subjects with mild asthma up-regulated more genes with greater overall variability in response to IL-17A than from healthy donors. Finally, in response to IL-17A, ASM cells displayed rapid activation of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway and increased nuclear levels of phosphorylated extracellular signal-regulated kinase. Taken together, our results suggest that IL-17A mediated modest gene expression response, which, in cooperation with the NF-kappa B signaling network, may regulate the gene expression profile in ASM cells.
引用
收藏
页码:1053 / 1063
页数:11
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