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 gp130(F/F) mouse model for spontaneous pulmonary inflammation and emphysema. METHODS: The expression of Th17-related factors was quantified in the lungs of gp130(F/F) mice and emphysematous patients, and the degree of pulmonary inflammation and emphysema was measured in gp130(F/F) : Il17a-/- mice by immunohistochemistry, stereology and respiratory mechanics. RESULTS: In gp130(F/F) mice, lung gene expression of Il17a and other Th17-related factors was augmented compared with gp130+/+ (wild-type), gp130(F/F) : Il6-/- and gp130(F/F) : Stat3-/+ mice displaying normalized Stat3 activity and no lung inflammation. Importantly, genetic ablation of Il17a in gp130(F/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 gp130(F/F) mice compared with gp130(F/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.
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 gp130(F/F)mouse model for spontaneous pulmonary inflammation and emphysema. METHODS: The expression of Th17-related factors was quantified in the lungs of gp130(F/F)mice and emphysematouspatients, and the degree of pulmonary inflammation and emphysema was measured in gp130(F/F) : Il17a-/- mice by immunohistochemistry, stereology and respiratory mechanics. RESULTS: In gp130(F/F)mice, lung gene expression of Il17a and other Th17-related factors was augmented compared with gp130+/+ (wild-type), gp130(F/F) : Il6-/- and gp130(F/F) : Stat3-/+ mice displaying normalized Stat3 activity and no lung inflammation. Importantly, genetic ablation of Il17a in gp130(F/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 gp130(F/F)mice compared with gp130(F/F) : Il17a-/- and gp130+/+ mice. Consistent with these findings, augmented IL17A expression was observed in emphysemapatients 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.
Authors: Shehla S Razvi; Jeremy B Richards; Farhan Malik; Kevin R Cromar; Roger E Price; Cynthia S Bell; Tingting Weng; Constance L Atkins; Chantal Y Spencer; Katherine J Cockerill; Amy L Alexander; Michael R Blackburn; Joseph L Alcorn; Ikram U Haque; Richard A Johnston Journal: Am J Physiol Lung Cell Mol Physiol Date: 2015-09-18 Impact factor: 5.464
Authors: Maysa Alves Rodrigues Brandao-Rangel; Andre Luis Lacerda Bachi; Manoel Carneiro Oliveira-Junior; Asghar Abbasi; Adriano Silva-Renno; Auriléia Aparecida de Brito; Ana Paula Ligeiro de Oliveira; Alessandra Choqueta Toledo-Arruda; Maria Gabriela Belvisi; Rodolfo Paula Vieira Journal: Oxid Med Cell Longev Date: 2017-10-18 Impact factor: 6.543
Authors: Larissa E F Silva; Juliana D Lourenço; Kaique R Silva; Fernanda Paula R Santana; Júlia B Kohler; Alyne R Moreira; Ana Paula P Velosa; Carla M Prado; Rodolfo P Vieira; Marcelo V Aun; Iolanda Fátima L C Tibério; Juliana T Ito; Fernanda D T Q S Lopes Journal: Sci Rep Date: 2020-09-17 Impact factor: 4.379