Monocyte Chemotactic Protein-Induced Protein 1 (MCPIP-1): A Key Player of Host Defense and Immune Regulation

Zhuqing Jin,Candice Sareli,Pappachan E Kolattukudy,En Zheng,Jianli Niu

doi:10.3389/fimmu.2021.727861

Abstract

Inflammatory response is a host-protective mechanism against tissue injury or infections, but also has the potential to cause extensive immunopathology and tissue damage, as seen in many diseases, such as cardiovascular diseases, neurodegenerative diseases, metabolic syndrome and many other infectious diseases with public health concerns, such as Coronavirus Disease 2019 (COVID-19), if failure to resolve in a timely manner. Recent studies have uncovered a superfamily of endogenous chemical molecules that tend to resolve inflammatory responses and re-establish homeostasis without causing excessive damage to healthy cells and tissues. Among these, the monocyte chemoattractant protein-induced protein (MCPIP) family consisting of four members (MCPIP-1, -2, -3, and -4) has emerged as a group of evolutionarily conserved molecules participating in the resolution of inflammation. The focus of this review highlights the biological functions of MCPIP-1 (also known as Regnase-1), the best-studied member of this family, in the resolution of inflammatory response. As outlined in this review, MCPIP-1 acts on specific signaling pathways, in particular NFκB, to blunt production of inflammatory mediators, while also acts as an endonuclease controlling the stability of mRNA and microRNA (miRNA), leading to the resolution of inflammation, clearance of virus and dead cells, and promotion of tissue regeneration via its pleiotropic effects. Evidence from transgenic and knock-out mouse models revealed an involvement of MCPIP-1 expression in immune functions and in the physiology of the cardiovascular system, indicating that MCPIP-1 is a key endogenous molecule that governs normal resolution of acute inflammation and infection. In this review, we also discuss the current evidence underlying the roles of other members of the MCPIP family in the regulation of inflammatory processes. Further understanding of the proteins from this family will provide new insights into the identification of novel targets for both host effectors and microbial factors and will lead to new therapeutic treatments for infections and other inflammatory diseases.

Highlights

Inflammatory response is an immunological defense mechanism of the host to infections and tissue damage or stress [1]
We summarized the relevant literature about the role of monocyte chemoattractant protein-induced protein (MCPIP) family proteins, in particular MCPIP-1, in the regulation of inflammatory response in different stress conditions
In vivo and in vitro studies revealed that MCPIP-1 expression by immune and non-immune cells contributes to the resolution of inflammation through distinct cellular and molecular programs

Summary

Introduction

Inflammatory response is an immunological defense mechanism of the host to infections and tissue damage (e.g., ischemic insults) or stress [1]. Emerging evidence indicates that MCPIP-1 plays an essential role in the regulation of inflammatory response, with additional roles in defense against viruses and various stresses, cellular differentiation, and apoptosis [13, 14], all of these are key cellular and molecular components that contribute to the successful resolution of inflammation [9, 10, 15,16,17,18]. Macrophages from MCPIP-1deficient mice showed up-regulation of pro-inflammatory mediators together with a greatly increased ubiquitination of TRAFs (TNF receptor–associated factors) and the receptorinteracting protein (RIP) kinases, both of which play a central role in the LPS-, IL-1b- and TNF-induced activation of NFkB signaling pathway [46].

Results

Conclusion