IL-17A contributes to myocardial ischemic injury by activating NLRP3 inflammasome in macrophages through AMPKα/p38MAPK/ERK1/2 signal pathway in mice.

Abstract

BACKGROUND:

Acute myocardial infarction (AMI) is followed by an acute inflammation involving inflammasome activation, thereby inducing cardiac dysfunction. Interleukin-17A (IL-17A) involves in many inflammatory diseases, but its roles in inflammation following AMI are still obscure. The aim of this study is to investigate the roles of IL-17A in the inflammatory response following AMI and its underlying mechanisms.

METHODS AND RESULTS:

NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway were significantly activated under the induction of IL-17A in mouse peritoneal macrophages, which could be inhibited by AMPK inhibitor compound C (CC). Both p38MAPK and ERK1/2 inhibitors could partially inhibit the activation of NLRP3 inflammasome in macrophages treated by IL-17A. In vivo, IL-17A knockout not only decreased the infiltration of macrophages and the activation of NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway in ischemic myocardium, but also improved cardiac function and reduced infarction size after the ligation of descending segment from left coronary artery for 3 days in mice, while IL-17A administration further aggravated the myocardial ischemic injury, which were prevented by CC administration.

CONCLUSION:

IL-17A aggravates inflammatory response during AMI by inducing macrophages infiltration and activating NLRP3 inflammasome through AMPKα/p38MAPK/ERK1/2 pathway.

• Authors: Lisha Zhang, Peining Liu, Wen Wen, Xiaofang Bai, Yan Zhang, Mengping Liu, Lijun Wang, Yue Wu, Zuyi Yuan, Juan Zhou
• Journal: Molecular immunology (Mol Immunol) Vol. 105 Pg. 240-250 (01 2019) ISSN: 1872-9142 [Electronic] England
• PMID: 30562644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Ltd.

Chemical References

• Il17a protein, mouse
• Inflammasomes
• Interleukin-17
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Mapk1 protein, mouse
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics, immunology)
• Animals
• Inflammasomes (genetics, immunology)
• Interleukin-17 (genetics, immunology)
• MAP Kinase Signaling System (genetics, immunology)
• Macrophages, Peritoneal (immunology, pathology)
• Mice
• Mice, Knockout
• Mitogen-Activated Protein Kinase 1 (genetics, immunology)
• Mitogen-Activated Protein Kinase 3 (genetics, immunology)
• Myocardial Ischemia (genetics, immunology, pathology)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, immunology)
• p38 Mitogen-Activated Protein Kinases (genetics, immunology)