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

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.

Macrophage-Specific MCPIP1/Regnase-1 Attenuates Kidney Ischemia-Reperfusion Injury by Shaping the Local Inflammatory Response and Tissue Regeneration

“…In line with various studies, MCPIP1 negatively regulates TLR-mediated inflammation and may significantly affect the course of ischemic injury followed by regeneration [39,40]. We, therefore, induced unilateral renal IRI for 30 min in wild-type and cell-specific (LysM) Mcpip1 knockouts to assess kidney outcomes after 3 and 30 days upon injury (early and chronic stage of injury).…”

Localization and expression profiles of gingival monocyte chemoattractant protein-1-induced protein-1 (MCPIP-1) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT-1)

“…Post-transcriptional processes, including RNA cleavage, regulate the activation and resolution of the immune system [1,2]. Monocyte chemotactic protein-1-induced protein-1 (MCPIP-1/Regnase-1), which was originally detected in MCP-1-treated human peripheral blood monocytes through microarrays, is a ribonuclease (RNase) and negatively regulates inflammatory responses [3,4].…”

“…MCPIP-1 as a RNase participates in the post-transcriptional regulation of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and IL-8 [6][7][8]. Furthermore, MCPIP-1 drives the resolution process of inflammation by suppression of nuclear factor kappa B (NFkB) activation, stimulation of the damaged cell clearance via apoptosis, and promoting anti-inflammatory macrophage phenotype polarization [2]. It has also a negative feedback system that reduces Regnase-1 mRNA expression in the presence of high levels of Regnase-1 protein [1].…”

Regulation of gingival keratinocyte monocyte chemoattractant protein‐1‐induced protein (MCPIP)‐1 and mucosa‐associated lymphoid tissue lymphoma translocation protein (MALT)‐1 expressions by periodontal bacteria, lipopolysaccharide, and interleukin‐1β

“…MCPIP‐1 acts as a broad suppressor of miRNA activity and biogenesis 11 . Its involvement in the deubiquitination process provides inhibition of LPS and IL‐1‐induced NF‐kB signaling pathway, whereas its RNase activity suppresses proinflammatory cytokine (IL‐6, IL‐1β, or IL‐8) mRNA activity 12–16 . Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT‐1) is a cysteine protease that cleaves the inflammatory signaling suppressors and eventually activates immune cells.…”

“… 11 Its involvement in the deubiquitination process provides inhibition of LPS and IL‐1‐induced NF‐kB signaling pathway, whereas its RNase activity suppresses proinflammatory cytokine (IL‐6, IL‐1β, or IL‐8) mRNA activity. 12 , 13 , 14 , 15 , 16 Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT‐1) is a cysteine protease that cleaves the inflammatory signaling suppressors and eventually activates immune cells. MALT‐1 suppression can cause inflammatory genes to synthesize cytokines (MCPIP‐1 included) and inflammation develops in the absence of MALT‐1.…”