Role of IL-37 in Cardiovascular Disease Inflammation

Yang, Ziyi; Kang, Lin; Wang, Yan; Xiang, Jiaqing; Wu, Qianying; Xu, Caimin; Zhou, Yanqing; Chen, Shaoyuan; Fang, Hongcheng; Liu, Jie; Dong, Ming

doi:10.1016/j.cjca.2019.04.007

Cited by 28 publications

(17 citation statements)

References 68 publications

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“…However, as described above, IL-37 plays an important anti-inflammatory and immunomodulatory capacity in a variety of inflammatory and autoimmune diseases. In addition, IL-37 in vivo could inhibit NLRP3 activation also be mentioned in colitis and LPS-induced disease [19,22,[35][36][37]. In recent study, Rudloff et al reported that IL-37 significantly suppress inflammasome activity in vivo to ameliorate inflammasome-driven diseases, which could corroborate our study results to some extent [38].…”

Section: Discussionsupporting

confidence: 90%

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

Kong

et al. 2020

Preprint

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Background: Ischemia reperfusion injury (IRI) is the major cause of intestinal damage in clinic. Although either mesenchymal stromal cells (MSCs) or interleukin 37 (IL-37) showed some beneficial roles to ameliorate IRI, their effects are limited. In this study, the protective effects of IL-37 gene-modified MSCs (IL-37-MSCs) for better prevention of intestinal IRI are investigated.Methods: Intestinal IRI model was established by occluding the superior mesenteric artery for 30min and then reperfusing for 72 hours in rats. Forty adult male SD rats were randomly divided into sham control, IL-37-MSC-treated, MSC-treated, recombinant IL-37 (rIL-37)-treated and untreated groups. Intestinal damage was assessed by H&E staining. The levels of gut barrier function factors (diamine oxidase and D-Lactate) and inflammation reactivity cytokine IL-1β were assayed by ELISA. The expressions of tissue damage-related NLRP3 inflammasome and relative proteins including clevead caspase-1, IL-1β and IL-18 were detected by western blot. As downstream of IL-1β and IL-18, the mRNA levels of proinflammatory mediators IL-6 and TNF-α were determined by qPCR. Data were analyzed by one-way analysis of variance among groups.Results: IL-37-MSCs were able to migrate to the damaged tissue and significantly inhibit intestinal IRI. As compared with MSCs or rIL-37 monotherapy group, IL-37-MSC treatment not only improved gut barrier function but also decreased local and systemic inflammation reactivity cytokine IL-1β level in IRI rats. In addition, tissue damage-related NLRP3 and relative proteins (cleaved caspase-1, IL-1β and 4 IL-18) were significantly decreased in IRI rats treated with IL-37-MSCs. Furthermore, IL-1β and IL-18 related proinflammatory mediators IL-6 and TNF-α mRNA expressions were markedly decreased following IL-37-MSC treatment.Conclusion: The results suggest that IL-37 gene modification significantly enhance the protective effects of MSCs against intestinal IRI. In addition, NLRP3-related signaling pathways could be associated with IL-37-MSC mediated protection.

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Section: Discussionsupporting

confidence: 90%

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

Kong

et al. 2020

Preprint

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“…The accumulation of oxidized LDL (ox-LDL) in macrophages of these mice could be attenuated by AMPK through the regulation of the expression of cholesterol flow mediators as the cassette transporter of ATP binding A1 (ABCA1) and G1 (ABCG1) [ 12 ]. It is well-known that high levels of cholesterol are a risk factor for atherosclerosis, and recently it was reported that treatment with IL-37 recombinant diminishes the accumulation of lipids and the foam cells’ formation into the atherosclerotic plaque, as regulated by the transcription factor Smad3 [ 29 , 30 ]. In the same way, the nine polymorphisms were in linkage disequilibrium, and one of the formed haplotypes ( ATCCTGTCA ) was associated with a low risk of HC.…”

Section: Discussionmentioning

confidence: 99%

IL-37 Gene and Cholesterol Metabolism: Association of Polymorphisms with the Presence of Hypercholesterolemia and Cardiovascular Risk Factors. The GEA Mexican Study

et al. 2020

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Interleukin 37 (IL-37) is an anti-inflammatory cytokine involved in the regulation of cholesterol homeostasis, reducing the levels of plasma cholesterol, fatty acids, and triglycerides. The aim of the present study was to evaluate the association of the IL-37 polymorphisms with the presence of hypercholesterolemia (HC), and with cardiovascular risk factors. Nine IL-37 polymorphisms (rs2708965, rs2708962, rs6717710, rs2708961, rs2708960, rs2708958, rs2723187, rs2708947, and rs2723192) were determined by TaqMan assays in a group of 1292 individuals (514 with and 778 without hypercholesterolemia) belonging to the cohort of the GEA Mexican Study. The associations were evaluated by logistic regression, using inheritance models adjusted by confounding variables. Under codominant 1 model, the rs2708961 (OR = 0.51, p = 0.02), rs2723187 (OR = 0.35, p = 0.005), and rs2708947 (OR = 0.49, p = 0.02) polymorphisms were associated with low risk of HC. The association of the polymorphisms with cardiovascular risk factors was evaluated independently in HC and non-HC individuals. In non-HC individuals, some polymorphisms were associated with the risk of having high levels of LDL-C, glucose, and high risk of T2DM, and low risk of having high visceral abdominal fat. On the other hand, in individuals with HC five, polymorphisms were associated with high levels of C-reactive protein. The IL-37 rs2708961, rs2723187, rs2708947 polymorphisms were associated with low risk of HC, and some IL-37 polymorphisms were associated with cardiometabolic factors in both individuals with and without HC.

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“…To explore the specific mechanism of action of IL‐37b in inflammation, it was important to know the mechanism through which receptor complex IL‐37b works. IL‐37b can bind to IL‐1R8 to involve in allergic airway inflammation, asthma and atherosclerosis . Therefore, we hypothesized that IL‐1R8 is required for IL‐37b to downregulate inflammation in TMJ.…”

Section: Discussionmentioning

confidence: 99%

“…IL-37b can bind to IL-1R8 to involve in allergic airway inflammation, 25 asthma 35,36 and atherosclerosis. 37 Therefore, we hypothesized that IL-1R8 is required for IL-37b to downregulate inflammation in TMJ. Here, IL-1R8 was knocked-down and assessed by qRT-PCR.…”

Section: Discussionmentioning

confidence: 99%

IL‐37b alleviates inflammation in the temporomandibular joint cartilage via IL‐1R8 pathway

et al. 2019

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Objectives Interleukin (IL)‐37 is a natural suppressor of innate inflammation. This study was conducted to explore the anti‐inflammatory effects of IL‐37 in temporomandibular joint (TMJ) inflammation. Materials and Methods The expression of IL‐37 in the TMJ was measured using ELISA and IHC. Human TMJ chondrocytes were treated with IL‐37b and IL‐1β, and inflammation‐related factors were detected. siRNA‐IL‐1R8 was transfected into chondrocytes, and the affected pathways were detected. IL‐37b was used in disc‐perforation‐induced TMJ inflammation in SD rats. Micro‐CT, IHC, real‐time PCR and histological staining were used to quantify the therapeutic effect of IL‐37b. Results IL‐37 was expressed in the synovium and the disc of patients with osteoarthritis (OA) and in the articular cartilage of condylar fracture patients. IL‐37 was highly expressed in synovial fluid of patients with synovitis than in those with OA and disc displacement and was closely related to visual analogue scale (VAS) score. In vitro, IL‐37b suppressed the expression of pro‐inflammatory factors. In addition, IL‐37b exerted anti‐inflammatory effects via IL‐1R8 by inhibiting the p38, ERK, JNK and NF‐κB activation, while silencing IL‐1R8 led to inflammation and upregulation of these signals. In disc‐perforation‐induced TMJ inflammation in SD rats, IL‐37b suppressed inflammation and inhibited osteoclast formation to protect against TMJ. Conclusions IL‐37b may be a novel therapeutic agent for TMJ inflammation.

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Role of IL-37 in Cardiovascular Disease Inflammation

Cited by 28 publications

References 68 publications

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

IL-37 Gene and Cholesterol Metabolism: Association of Polymorphisms with the Presence of Hypercholesterolemia and Cardiovascular Risk Factors. The GEA Mexican Study

IL‐37b alleviates inflammation in the temporomandibular joint cartilage via IL‐1R8 pathway

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