Taurine Alleviates Sympathetic Innervation by Inhibiting NLRP3 Inflammasome in Postinfarcted Rats.

Abstract

ABSTRACT:

The NLRP3 inflammasome is activated by myocardial infarction and then induces the activation of inflammatory caspase-1 activation and maturation of IL-1β, a regulator of synthesis of the nerve growth factor (NGF). Here, we studied whether taurine, 2-aminoethanesulphonic acid, can attenuate cardiac sympathetic reinnervation by modulating NLRP3 inflammasome-mediated NGF in a rat model of myocardial infarction. Male Wistar rats were subjected to coronary ligation and then randomized to either saline or taurine for 3 days or 4 weeks. Postinfarction was associated with activation of NF-κB (p65) and NLRP3 inflammasome component and increased the protein and expression of IL-1β. Macrophages at the border zone were shown to be positive for IL-1β 3 days postinfarction. Compared with vehicle, infarcted rats treated with taurine significantly attenuated myocardial messenger RNA and protein levels of NF-κB, NLRP3 inflammasome, mature caspase-1, and IL-1β. Immunofluorescent analysis, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting of NGF showed that sympathetic hyperinnervation was blunted after administering taurine. Arrhythmia vulnerability in the taurine-treated infarcted rats was significantly improved than those in vehicle. Ex vivo studies showed that taurine infusion reduced myocardial IL-1β level at the extent similar to either pyrrolidine dithiocarbamate or CP-456,773, inhibitors of NF-κB and NLRP3 inflammasome, implying the key axis of NF-κB/NLRP3 inflammasome in mediating taurine-related anti-inflammation. Furthermore, administration of anti-IL-1β antibody reduced NGF levels. Taurine attenuated sympathetic innervation mainly by NLRP3 inflammasome/IL-1β-dependent pathway, which downregulated expression of NGF in infarcted rats. These findings may provide a new insight into the anti-inflammation effect of taurine.

• Authors: Cheng-Che Lee, Wei-Ting Chen, Syue-Yi Chen, Tsung-Ming Lee
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 77 Issue 6 Pg. 745-755 (04 15 2021) ISSN: 1533-4023 [Electronic] United States
• PMID: 34057159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Chemical References

• Anti-Inflammatory Agents
• IL1B protein, rat
• Inflammasomes
• Interleukin-1beta
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Transcription Factor RelA
• Taurine

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Disease Models, Animal
• Inflammasomes (drug effects, metabolism)
• Inflammation (drug therapy, pathology)
• Interleukin-1beta (immunology)
• Macrophages (metabolism)
• Male
• Myocardial Infarction (drug therapy, physiopathology)
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Random Allocation
• Rats
• Rats, Wistar
• Sympathetic Nervous System (drug effects, physiopathology)
• Taurine (pharmacology)
• Transcription Factor RelA (metabolism)