The emerging role of interleukin‐37 in cardiovascular diseases

Abstract

IntroductionInterleukin (IL)‐37 is a newly identified member of the IL‐1 family, and shows a growing role in a variety of diseases. This review aims at summarizing and discussing the role of IL‐37 in cardiovascular diseases.MethodsData for this review were identified by searches of MEDLINE, Embase, and PubMed using appropriate search terms.ResultsIL‐37 is a newly identified cytokine belonging to the IL‐1 family and is expressed in inflammatory immune cells and several parenchymal cells. It has potent anti‐inflammatory and immunosuppressive properties, with two mechanisms underlying this function. IL‐37 is produced as a precursor and then cleaved into mature form in the cytoplasm by caspase‐1, translocating to nucleus and suppressing the transcription of several pro‐inflammatory genes by binding SMAD‐3. Besides, IL‐37 can be secreted extracellularly, and binds to IL‐18Ra chain and recruits Toll/IL‐1R (TIR)‐8 for transducing anti‐inflammatory signaling. IL‐37 is upregulated in an inducible manner and negatively regulates signaling mediated by TLR agonists and pro‐inflammatory cytokines. The cytokine has been shown to inhibit both innate and adaptive immunological responses, exert antitumor effects, and act as a prognostic marker in a variety of autoimmune diseases.ConclusionsRecent studies have suggested that IL‐37 plays a role in cardiovascular diseases. In this review, we provide an overview of the cytokine biology, discuss recent advances made in unraveling its cardio‐protective effects, and suggest guidelines for future research.

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

“…Our results show an enhanced expression of caspase-1 in mice with EAE that were treated with H-hPDLSCs-CM. IL-37, once translocated into the nucleus, prevents the transcription of proinflammatory cytokines and chemokines, such as IL-1α, IL-6, TNF, and CXCL2 (45, 47, 48). In agreement with this, we observed decreased levels of the proinflammatory cytokines, INF-γ and IL-17, after H-hPDLSCs-CM administration (37).…”

Extracellular IL-37 Enhances Osteogenic and Odontogenic Differentiation of Human Dental Pulp Stem Cells via Autophagy Pathway

“…The level of IL-37 is normally low, but this signi cantly increases under severe in ammatory conditions. It has been previously found that IL-37 plays an important regulatory role in the development of several in ammatory and autoimmune diseases [37,38]. Recent studies investigated that IL-37 mediates a variety of anti-cancer effects in multiple types of cancer [39].…”

Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets

“…Interleukin 37 (IL-37) is also known as IL-1 family member 7 (IL-1F7). The cytokine exists in its five splice variants (a-d), which were discovered and given different names in the past [337] , [338] . Of these splice variants, isoform b (or IL-37b) is the most prevalent and widely studied.…”

“…Although mice do not produce IL-37, human IL-37 functions as a potent anti-inflammatory cytokine. On one hand SIGIRR KO mice are hyper-responsive to LPS and other TLR agonists, on the other hand, IL-37 transgenic mice are relatively resistant to TLR agonists [337] , [338] . Inhibition of IL-37 activity by siRNA significantly increase the production of several pro-inflammatory mediators (IL-1β, IL-1α, GM-CSF, C-CSF, IL-6, and TNF-α) from human PBMCs when stimulated with either LPS or Pam3CSK4 [341] .…”