Cortistatin Inhibits NLRP3 Inflammasome Activation of Cardiac Fibroblasts During Sepsis.

Abstract

BACKGROUND:

Cortistatin is a recently discovered neuropeptide that has emerged as a potential endogenous antiinflammatory peptide. As a clinical syndrome, sepsis occurs when an infection becomes amplified, leading to organ dysfunction or risk for secondary infection. Human septic shock involves excessive inflammatory cytokine production. Interleukin (IL) 1β is one of these cytokines, and it plays a pivotal role in sepsis-induced myocardial dysfunction. The aim of the present study is to evaluate whether cortistatin inhibits nucleotide-binding oligomerization domain-like receptor with a pyrin-domain 3 (NLRP3) inflammasome/caspase-1/IL-1β pathway in cardiac fibroblasts (CFs) and whether this role can subsequently affect myocardial injury.

METHODS AND RESULTS:

To test these processes, a murine model of cecal ligation and puncture in vivo and lipopolysaccharide-induced cardiac fibroblasts were used in vitro. We found that pretreatment with cortistatin inhibited NLRP3-mediated ASC pyroptosome formation, caspase-1 activation, and IL-1β secretion. Additionally cortistatin inhibits proinflammatory pathways (nuclear factor κB and pro-IL-1β).

CONCLUSIONS:

This work provided the first evidence of cortistatin as a new immunomodulatory factor with the capacity to deactivate NLRP3 inflammasome activity and to protect against the myocardial injury induced by sepsis. This study has important implications for the design of new strategies to control NLRP3-related diseases.

• Authors: Bo Zhang, Yue Liu, Yu-Bin Sui, Huai-Qiu Cai, Wen-Xiu Liu, Minling Zhu, Xin-Hua Yin
• Journal: Journal of cardiac failure (J Card Fail) Vol. 21 Issue 5 Pg. 426-433 (May 2015) ISSN: 1532-8414 [Electronic] United States
• PMID: 25639691 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Carrier Proteins
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neuropeptides
• Nlrp3 protein, rat
• Peptides, Cyclic
• cortistatin 14

Topics

• Animals
• Carrier Proteins (antagonists & inhibitors, metabolism)
• Cells, Cultured
• Fibroblasts (drug effects, metabolism)
• Inflammasomes (antagonists & inhibitors, metabolism)
• Male
• Myocytes, Cardiac (drug effects, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neuropeptides (pharmacology, therapeutic use)
• Peptides, Cyclic (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Sepsis (drug therapy, metabolism)