Abstract
Activation of α-7 nicotinic acetylcholine receptor (α7nAChR) receptor might induce cardiac inflammation, cardiac remodeling, and dysfunction. In this regard, this study aims to clarify the role and mechanism of α7nAChR in the process of cardiac inflammation and damage. Normal male C57BL/6J and NLRP3-knockout mice were used to evaluate the effect of PHA-543613, a selective agonist of α7nAChR, on cardiac inflammation and possible involvement of NLRP3/Caspase-1/IL-18 using western blotting and ELISA. Activation of α7nAChR using PHA-543613 (NE), at the doses of 0.5 mg/kg and 1 mg/kg, induced cardiac inflammation. In addition, both in vivo and in vitro studies showed higher expression of NLRP3 and higher activation of Caspase-1 and IL-18 after treating animals with NE. On the other hand, we did not observe any significant changes in inflammatory cytokines and cardiac inflammation after administration of NE in NLRP3-knockout mice. It could be concluded that blocking the NLRP3/Caspase-1/IL-18 pathway can simultaneously inhibit the inflammatory response mediated by α7nAChR and it would a novel target for inhibiting cardiac inflammation and remodeling.
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Acknowledgements
The research is supported by The Scientific Research Project in 2017 of Hunan Provincial Education Department “Intrauterine origin of GR/MR-mediated cardiac injury induced by dexamethasone exposure during pregnancy in rats” (17C1482) and The Scientific Research Project in 2017 of Xiangnan University “Effect of DEX overexposure during pregnancy on the expression of TRPM7 in fetal rat heart” (2017XJ24) and Characteristic Subjects of Pharmaceutical Application in Hunan Province (2018-469).
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ZG, BT, JW, WT, LP, YC, and JZ conceived and designed the study, collected subjects, performed experiments, analyzed the data and participated in the discussion, and wrote and revised the manuscript. All authors read and approved the final manuscript.
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Our study was in accordance with the National Institute of Health (NIH) Guidelines for the Care and Use of Laboratory Animals (HHS Publication 85-23, 1985), legislation for the protection of animals used for scientific purposes (Directive 2010/63/EU). Euthanasia was done using 7-min exposure to CO2 and followed by cervical dislocation for confirmation of death.
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Guo, Z., Tan, B., Wang, J. et al. Activation of α-7 Nicotinic Acetylcholine Receptor Attenuates Cardiac Inflammation Through NLRP3/Caspase-1/IL-18 Pathway. Biochem Genet 60, 1333–1345 (2022). https://doi.org/10.1007/s10528-021-10162-8
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DOI: https://doi.org/10.1007/s10528-021-10162-8