Myeloid cell-derived proteases produce a proinflammatory form of IL-37 that signals via IL-36 receptor engagement
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE214863 | GEO | 2022/10/12
REPOSITORIES: GEO
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Project description:Myeloid cell-derived proteases produce a proinflammatory form of IL-37 that signals via IL-36 receptor engagement
| PRJNA887411 | ENA
Project description:Interleukin (IL)-37 suppresses systemic and local inflammation. It is expressed in the epidermis, the external layer of the skin, and is decreased in inflammatory skin diseases including atopic dermatitis (AD) and psoriasis. Therefore, an agent applied topically on the skin that can increase IL-37 could be promising for treating AD and psoriasis; however, the mechanism regulating IL-37 remains largely unknown. Given that IL-37 expression is induced in differentiated keratinocytes, a major component of the epidermis, and that activation of aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, promotes keratinocyte differentiation, we hypothesized that AHR might be involved in the IL-37 expression in human keratinocytes. We analyzed normal epidermal human keratinocytes (NHEKs) treated with tapinarof and Galactomyces fermentation filtrate (GFF), which are potent AHR modulators. We found that tapinarof and GFF upregulated IL-37 in NHEKs, which was canceled by the knockdown of AHR using siRNA transfection, indicating that AHR mediates IL-37 expression in NHEKs. Furthermore, we found that the knockdown of IL-37 resulted in the upregulation of IL-33, an alarmin cytokine with crucial roles in the pathogenesis of AD and psoriasis. These findings suggest that IL-37 negatively regulates IL-33 expression in NHEKs. Finally, we examined whether tapinarof and GFF treatment modulates IL-33 expression in NHEKs. Such treatment inhibited IL-33 expression, which was partially reversed by the knockdown of either AHR or IL-37. Taken together, our findings provide the first evidence that tapinarof and GFF could have potential to prevent IL-33-overexpressing disorders such as AD and psoriasis via the AHR/IL-37 axis.
2021-12-31 | GSE181089 | GEO
Project description:Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here, we report that IL-37, a newly-described antiinflammatory member of the IL-1 family, affects obesity-induced inflammation and insulin resistance. IL-37 transgenic mice (IL-37tg) did not develop an obese phenotype in response to a high-fat diet (HFD). Unlike WT mice, IL-37tg mice exhibited reduced numbers of adipose tissue macrophages and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. A short-term HFD intervention revealed that the IL-37-mediated improvement in glucose tolerance is independent of bodyweight. IL-37tg mice manifested a beneficial metabolic profile with higher circulating levels of the anti-inflammatory adipokine adiponectin. In vitro treatment of differentiating adipocytes with recombinant IL-37 reduced adipogenesis. The beneficial effects of recombinant IL-37 involved activation of AMPK signaling. In humans, steady-state IL-37 adipose tissue mRNA levels were positively correlated with insulin sensitivity, lower adipose tissue levels of leptin and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.
2015-05-18 | GSE58952 | GEO
Project description:Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here, we report that IL-37, a newly-described antiinflammatory member of the IL-1 family, affects obesity-induced inflammation and insulin resistance. IL-37 transgenic mice (IL-37tg) did not develop an obese phenotype in response to a high-fat diet (HFD). Unlike WT mice, IL-37tg mice exhibited reduced numbers of adipose tissue macrophages and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. A short-term HFD intervention revealed that the IL-37-mediated improvement in glucose tolerance is independent of bodyweight. IL-37tg mice manifested a beneficial metabolic profile with higher circulating levels of the anti-inflammatory adipokine adiponectin. In vitro treatment of differentiating adipocytes with recombinant IL-37 reduced adipogenesis. The beneficial effects of recombinant IL-37 involved activation of AMPK signaling. In humans, steady-state IL-37 adipose tissue mRNA levels were positively correlated with insulin sensitivity, lower adipose tissue levels of leptin and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes. Gene arrays were performed on epidydimal white adipose tissue samples from wild type and human IL37-overexpressing transgenic mice fed a high fat diet for 16 weeks.
2015-05-18 | E-GEOD-58952 | biostudies-arrayexpress
Project description:IL-37 negatively regulates IL-33 expression in human keratinocytes
| PRJNA750665 | ENA
Project description:We performed whole microarray expressiong prolife of Sk-hep1 cells which could over-express IL-37. This project is to explore the effect of interleukin-37 on hepatocellular carcinoma(HCC) development. We transfected human HCC cell line Sk-hep1 with lentiviral vector encoding IL-37 or control. The successfully transfected cells were sorted by FACS and the cells were further cultured for 24 hours. The cells were harvested and send for microarray analysis.
2020-02-06 | GSE144728 | GEO
Project description:BackgroundInterleukin (IL)-36 cytokines are recently reported member of the IL-1 cytokine family. However, there is little information regarding the association between IL-36 cytokines and gut inflammation. In the present study, we investigated the biological activity of IL-36? and IL-36? using human colonic subepithelial myofibroblasts (SEMFs).MethodsThe mRNA expression and the protein expression of target molecules in SEMFs were evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The intracellular signaling of IL-36 cytokines was analyzed using Western blot analysis and small interfering RNAs (siRNAs) specific for MyD88 adaptor proteins (MyD88 and IRAK1) and NF-?B p65.ResultsIL-36? and IL-36? significantly enhanced the secretion of IL-6 and CXC chemokines (CXCL1, CXCL2, and CXCL8) by SEMFs. The combination of IL-36?/? and IL-17A or of IL-36?/? and tumor necrosis factor-? showed a synergistic effect on the induction of IL-6 and CXC chemokines. The mRNA expression of proinflammatory mediators induced by IL-36? and/or IL-36? was significantly suppressed by transfection of siRNA for MyD88 or IRAK1. Both inhibitors of mitogen activated protein kinases and siRNAs specific for NF-?Bp65 significantly reduced the expression of IL-6 and CXC chemokines induced by IL-36? and/or IL-36?.ConclusionThese results suggest that IL-36? and IL-36? contribute to gut inflammation through the induction of proinflammatory mediators.
| S-EPMC4585048 | biostudies-literature
Project description:IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we performed single-cell RNA-seq on an acute LPS mouse model of lung inflammation to provide insights into the intercellular signaling pathways and mechanisms through which IL-36 promotes lung inflammation. We identified neutrophils as a source of IL-36 which provides a rationale for targeting IL-36 to improve treatment of a variety of neutrophilic lung diseases.
2021-01-25 | GSE159161 | GEO
Project description:The effect of IL-37 in HCC cell line Sk-hep1
| PRJNA604931 | ENA
Project description:IL-37 reduces allergic inflammation of atopic dermatitis by regulating gut microbiota
| PRJEB36050 | ENA