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- Title
IL-6/Stat3-driven pulmonary inflammation, but not emphysema, is dependent on interleukin-17 A in mice.
- Authors
Ruwanpura, Saleela M.; McLeod, Louise; Brooks, Gavin D.; Bozinovski, Steven; Vlahos, Ross; Longano, Anthony; Bardin, Philip G.; Anderson, Gary P.; Jenkins, Brendan J.
- Abstract
Background and objective Pulmonary emphysema is linked to T cell-mediated autoimmune inflammation, although the pathogenic role of specific pro-inflammatory cytokines remains unclear. The Th17 type response, characterized by the production of the cytokine interleukin ( IL)- 17A, is modulated in part by the IL-6/signal transducer and activator of transcription ( Stat)3 signalling axis and is associated with numerous autoimmune diseases. We therefore evaluated a causal role for IL- 17A in the IL-6-driven gp130F/F mouse model for spontaneous pulmonary inflammation and emphysema. Methods The expression of Th17-related factors was quantified in the lungs of gp130F/F mice and emphysematous patients, and the degree of pulmonary inflammation and emphysema was measured in gp130F/F : Il17a−/− mice by immunohistochemistry, stereology and respiratory mechanics. Results In gp130F/F mice, lung gene expression of Il17a and other Th17-related factors was augmented compared with gp130 +/+ (wild-type), gp130F/F : Il6−/− and gp130F/F : Stat3−/+ mice displaying normalized Stat3 activity and no lung inflammation. Importantly, genetic ablation of Il17a in gp130F/F : Il17a−/− mice prevented lung inflammation; however, emphysema still developed. Additionally, messenger RNA expression of inflammatory genes Cxcl1, Cxcl2, Ccl2 and Tnfα; as well as Il6 and the Stat3-target gene, Socs3, were upregulated in the lungs of gp130F/F mice compared with gp130F/F : Il17a−/− and gp130+/+ mice. Consistent with these findings, augmented IL17A expression was observed in emphysema patients presenting with inflammation compared with inflammation-free individuals. Conclusions Collectively, our data suggest that the integration of IL- 17A into the IL-6/ Stat3 signalling axis mediates lung inflammation, but not emphysema, and that discrete targeting of IL- 17A may alleviate pulmonary inflammatory-related diseases.
- Subjects
PULMONARY emphysema; AUTOIMMUNE diseases; T cells; INTERLEUKIN-6; CELLULAR signal transduction
- Publication
Respirology, 2014, Vol 19, Issue 3, p419
- ISSN
1323-7799
- Publication type
Article
- DOI
10.1111/resp.12243