Dual interleukin-17A/F deficiency protects against acute and chronic response to cigarette smoke exposure in mice
| Autor: | Shin-Ichi Inoue, Kazuhiro Ito, Masuo Nakamura, Shigeru Kamiya, Peter J. Barnes, Fumie Kobayashi, Hiroshi Kamma, Tomoko Hanawa, Hajime Takizawa, Akihiko Kudo, Yoichiro Iwakura, Hiroo Wada |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Chemokine Neutrophils Diseases Pathogenesis Mice Pulmonary Disease Chronic Obstructive 0302 clinical medicine Medicine Macrophage Lung COPD Multidisciplinary medicine.diagnostic_test biology Interleukin-17 medicine.anatomical_structure Matrix Metalloproteinase 9 Acute Disease Cytokines Female Interleukin 17 Cell biology medicine.medical_specialty Science Article Cigarette Smoking 03 medical and health sciences Medical research Internal medicine Animals business.industry Macrophages Colony-stimulating factor medicine.disease Mice Mutant Strains Environmental sciences 030104 developmental biology Bronchoalveolar lavage Endocrinology Gene Expression Regulation 030228 respiratory system Chronic Disease biology.protein business |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | IL-17A and IL-17F are both involved in the pathogenesis of neutrophilic inflammation observed in COPD and severe asthma. To explore this, mice deficient in both Il17a and Il17f and wild type (WT) mice were exposed to cigarette smoke or environmental air for 5 to 28 days and changes in inflammatory cells in bronchoalveolar lavage (BAL) fluid were determined. We also measured the mRNA expression of keratinocyte derived chemokine (Kc), macrophage inflammatory protein-2 (Mip2), granulocyte–macrophage colony stimulating factor (Gmcsf) and matrix metalloproteinase-9 (Mmp9 ) in lung tissue after 8 days, and lung morphometric changes after 24 weeks of exposure to cigarette smoke compared to air-exposed control animals. Macrophage counts in BAL fluid initially peaked at day 8 and again on day 28, while neutrophil counts peaked between day 8 and 12 in WT mice. Mice dual deficient with Il17a and 1l17f showed similar kinetics with macrophages and neutrophils, but cell numbers at day 8 and mRNA expression of Kc, Gmcsf and Mmp9 were significantly reduced. Furthermore, airspaces in WT mice became larger after cigarette smoke exposure for 24 weeks, whereas this was not seen dual Il17a and 1l17f deficient mice. Combined Il17a and Il17f deficiency resulted in significant attenuation of neutrophilic inflammatory response and protection against structural lung changes after long term cigarette smoke exposure compared with WT mice. Dual IL-17A/F signalling plays an important role in pro-inflammatory responses associated with histological changes induced by cigarette smoke exposure. |
| Databáze: | OpenAIRE |
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