miR-223-3p contributes to suppressing NLRP3 inflammasome activation in Streptococcus equi ssp. zooepidemicus infection.

Abstract

Streptococcus equi subsp. zooepidemicus (SEZ) is an essential pathogen in a range of species, causing a worldwide variety of diseases, such as meningitis, endocarditis, and septicaemia. Studies have shown that microRNAs (miRNAs), which regulate target genes at the post-transcriptional level, play an important regulatory role in the organism. In this study, the infection of J774A.1 murine macrophages with SEZ up-regulated NLRP3 inflammasome and downstream pathways accompanied by miR-223-3p down-regulation. Through computational prediction and experimental confirmation, we have shown that miR-223-3p directly targets the NLRP3 mRNA. Consequently, overexpression of miR-223-3p suppressed NLRP3 inflammasome activation and downstream pathways in response to SEZ infection. The miR-223-3p inhibitor exhibited the opposite effect, causing hyperactivation of NLRP3 inflammation activation and downstream pathways. Additionally, we further demonstrated that miRNA-223-3p inhibited the secretion of IL-1β and IL-18 by regulating the NLRP3/caspase-1 pathway. Furthermore, intravenous administration of miR-223-3p significantly decreased inflammation in mice in response to SEZ. In conclusion, our results demonstrated that miR-223-3p contributes to suppressing the NLRP3 inflammasome activation in SEZ infection, contributing novel evidence to identify a therapeutic target for treating SEZ.

• Authors: Guochao Li, Xueqing Zong, Yun Cheng, Jianqi Xu, Jingfei Deng, Yunfei Huang, Chunquan Ma, Qiang Fu
• Journal: Veterinary microbiology (Vet Microbiol) Vol. 269 Pg. 109430 (Jun 2022) ISSN: 1873-2542 [Electronic] Netherlands
• PMID: 35427992 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Inflammasomes
• MIRN223 microRNA, mouse
• MicroRNAs
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse

Topics

• Animals
• Inflammasomes (genetics, metabolism)
• Inflammation (metabolism, veterinary)
• Mice
• MicroRNAs (genetics, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Streptococcal Infections (veterinary)
• Streptococcus equi (genetics, metabolism)