Dataset Information

IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice.

ABSTRACT:

Background

Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it's role in the inflammatory response of elastase-induced emphysema remains unclear.

Methods

In a model of elastase-induced pulmonary emphysema we examined the response of IL-17A-deficient mice, monitoring airway inflammation, static compliance, lung histology and levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid.

Results

Wild-type mice developed emphysematous changes in the lung tissue on day 21 after elastase treatment, whereas emphysematous changes were decreased in IL-17A-deficient mice compared to wild-type mice. Neutrophilia in BAL fluid, seen in elastase-treated wild-type mice, was reduced in elastase-treated IL-17A-deficient mice on day 4, associated with decreased levels of KC, MIP-2 and IL-1 beta. Elastase-treated wild-type mice showed increased IL-17A levels as well as increased numbers of IL-17A+ CD4 T cells in the lung in the initial period following elastase treatment.

Conclusions

These data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema. Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression.

SUBMITTER: Kurimoto E

PROVIDER: S-EPMC3564829 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Publications

IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice.

Kurimoto Etsuko E Miyahara Nobuaki N Kanehiro Arihiko A Waseda Koichi K Taniguchi Akihiko A Ikeda Genyo G Koga Hikari H Nishimori Hisakazu H Tanimoto Yasushi Y Kataoka Mikio M Iwakura Yoichiro Y Gelfand Erwin W EW Tanimoto Mitsune M

Respiratory research 20130120

<h4>Background</h4>Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it's role in the inflammatory response of elastase-induced emphysema remains unclear.<h4>Methods</h4>In a model of elastase-induced pulmonary emphysema we examined the response of IL-17A-deficient mice, monitoring airway inflammation, static compliance, lung histology and levels of neutrophil-related chemoki ...[more]

PMID: 23331548

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Project description:Interstitial lung disease, a common extra-articular complication of connective tissue disease, is characterized by progressive and irreversible pulmonary inflammation and fibrosis, which causes significant mortality. IL-22 shows a potential in regulating chronic inflammation and possibly plays an anti-fibrotic role by protecting epithelial cells. However, the detailed effects and underlying mechanisms are still unclear. In this study, we explored the impact of IL-22 on pulmonary fibrosis both in vivo and in vitro. To induce pulmonary fibrosis, wild-type mice and IL-22 knockout mice were intratracheally injected with bleomycin followed by treatments with recombinant IL-22 or IL-17A neutralizing antibody. We investigated the role of IL-22 on bleomycin-induced pulmonary fibrosis and the mechanism in the possible interaction between IL-22 and IL-17A. Fibrosis-related genes were detected using RT-qPCR, western blot, and immunofluorescence. Inflammatory and fibrotic changes were assessed based on histological features. We also used A549 human alveolar epithelial cells, NIH/3T3 mouse fibroblast cells, and primary mouse lung fibroblasts to study the impact of IL-22 on fibrosis in vitro. IL-22 knockout mice showed aggravated pulmonary fibrosis compared with wild-type mice, and injection of recombinant IL-22 decreased the severe fibrotic manifestations in IL-22 knockout mice. In cell culture assays, IL-22 decreased protein levels of Collagen I in A549 cells, NIH/3T3 cells, and primary mouse lung fibroblasts. IL-22 also reduced the protein level of Collagen I in NIH/3T3 cells which were co-cultured with T cells. Mechanistically, IL-22 reduced the Th17 cell proportion and IL-17A mRNA level in lung tissues, and treatment with an IL-17A neutralizing antibody alleviated the severe pulmonary fibrosis in IL-22 knockout mice. The IL-17A neutralizing antibody also reduced Collagen I expression in NIH/3T3 cells in vitro. Knockdown of IL-17A with siRNAs or administration of IL-22 in NIH/3T3 cells and MLFs decreased expression of Collagen I, an effect blocked by concurrent use of recombinant IL-17A. IL-22 mediated an anti-fibrogenesis effect in the bleomycin-induced pulmonary fibrosis model and this effect was associated with inhibition of IL-17A.

Dataset Information

IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice.

Background

Methods

Results

Conclusions

Publications

IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice.

Similar Datasets

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