Hydrodynamic delivery of IL-38 gene alleviates obesity-induced inflammation and insulin resistance

Xu, Keye; Sun, Jun; Chen, Sisi; Li, Yuan; Xiao, Peng; Li, Mingcai; Yan, Li

doi:10.1016/j.bbrc.2018.11.114

Cited by 26 publications

(16 citation statements)

References 24 publications

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“…Xu et al, 2018), diabetes (Liu, Chen, Zhou, Mu, & Liu, 2020), myocardial injury (Wei et al, 2020), and asthma (Matsuoka et al, 2019;Sun et al, 2020). Recently, we also found that IL-38 has the effect of inhibiting obesity-induced inflammation (K. Xu et al, 2019) and liver inflammatory damage (Yuan et al, 2016).…”

Section: Cell Ell B Biology Iology I International Nternationalmentioning

confidence: 68%

“…It has been reported that IL‐38 may play an anti‐inflammatory role in arthritis (Boutet et al, 2017), psoriasis (Han et al, 2019; Mercurio et al, 2018), systemic lupus erythematosus (Chu et al, 2017; Rudloff et al, 2015), inflammatory bowel disease (Xie et al, 2020), sepsis (Ge, Huang, Wu, Dong, & Yao, 2020; F. Xu et al, 2018), diabetes (Liu, Chen, Zhou, Mu, & Liu, 2020), myocardial injury (Wei et al, 2020), and asthma (Matsuoka et al, 2019; Sun et al, 2020). Recently, we also found that IL‐38 has the effect of inhibiting obesity‐induced inflammation (K. Xu et al, 2019) and liver inflammatory damage (Yuan et al, 2016).…”

Section: Introductionmentioning

confidence: 92%

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Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

Chen

Sun

et al. 2020

Cell Biology International

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Interleukin-38 (IL-38) is a novel member of the IL-1 cytokine family with anti-inflammatory activity. However, its effect on adipogenesis and inflammatory cytokines secretion of adipocytes in vitro has not been reported. To address whether IL-38 inhibits adipogenesis and inflammation in vitro, adipose precursor 3T3-L1 cells were cultured with or without IL-38. The morphology and size of lipid droplets in 3T3-L1 cells were measured by Oil red O staining. The mRNA expression levels of GATA-binding protein-3 (GATA-3), glucose transporter type 4 (GLUT4), peroxisome proliferator-associated receptor γ2, IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1) in 3T3-L1 cells were detected by real-time PCR, The contents of IL-6, IL-1β, and MCP-1 in 3T3-L1 cell medium supernatants were determined by enzyme-linked immunosorbent assay. IL-38 significantly decreased the number of lipid droplets in 3T3-L1 cells. IL-38 also increased GATA-3 and GLUT4 mRNA expression and inhibited IL-1β, IL-6, and MCP-1 secretion by 3T3-L1 cells. It is concluded that IL-38 can inhibit the differentiation of human adipocytes and inflammatory cytokine production by 3T3-L1 cells.

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Section: Cell Ell B Biology Iology I International Nternationalmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 92%

Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

Chen

Sun

et al. 2020

Cell Biology International

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“…In that study, patients with high serum concentrations of IL‐38 were more sensitive to lipid‐lowering therapy with atorvastatin [20]. In mice, overexpression of Il1f10 resulted in reduced hepatic fat accumulation, liver damage in high‐fat diet induced obesityand reduced adipocyte hypertrophy [33]. Together, human and mouse studies support the concept that high concentrations of IL‐38 are functional in suppressing inflammation, while low concentrations are a biomarker for cardiovascular and metabolic risk.…”

Section: Discussionmentioning

confidence: 99%

Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects

et al. 2020

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The IL‐1 family member IL‐38 (IL1F10) suppresses inflammatory and autoimmune conditions. Here, we report that plasma concentrations of IL‐38 in 288 healthy Europeans correlate positively with circulating memory B cells and plasmablasts. IL‐38 correlated negatively with age (p = 0.02) and was stable in 48 subjects for 1 year. In comparison with primary keratinocytes, IL1F10 expression in CD19+ B cells from PBMC was lower, whereas cell‐associated IL‐38 expression was comparable. In vitro, IL‐38 is released from CD19+ B cells after stimulation with rituximab. Intravenous LPS in humans failed to induce circulating IL‐38, compared to 100‐fold induction of IL‐6 and IL‐1 receptor antagonist. In a cohort of 296 subjects with body mass index > 27 at high risk for cardiovascular disease, IL‐38 plasma concentrations were significantly lower than in healthy subjects (p < 0.0001), and lowest in those with metabolic syndrome (p < 0.05). IL‐38 also correlated inversely with high sensitivity C‐reactive protein (p < 0.01), IL‐6, IL‐1Ra, and leptin (p < 0.05). We conclude that a relative deficiency of the B cell product IL‐38 is associated with increased systemic inflammation in aging, cardiovascular and metabolic disease, and is consistent with IL‐38 as an anti‐inflammatory cytokine.

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“…18 In addition, IL-38 can inhibit the production of the asthma-related Th17 cytokines IL-17 and IL-22, and preserve a low Th17 cell/regulatory T cell (Treg) balance. 19 In clinical and animal studies, we and other groups have reported aberrant IL-38 expression in many inflammatory diseases including allergic asthma, 20 rheumatoid arthritis, systemic lupus erythematosus (SLE), Crohn's disease, psoriasis, and chronic obstructive pulmonary disease (COPD) 21 , and the protective and anti-inflammatory roles of IL-38 in a murine model of arthritis, 22,23 SLE, 24 psoriasis, 25,26 obesity, 27 and sepsis. 28 Although IL-38 may be related to the IL-1R and IL-18R signaling pathways, the detailed intracellular signaling pathways involving IL-38 in eosinophil-mediated allergic inflammation have never been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma

et al. 2019

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We elucidated the anti-inflammatory mechanisms of IL-38 in allergic asthma. Human bronchial epithelial cells and eosinophils were cocultured upon stimulation with the viral RLR ligand poly (I:C)/LyoVec or infection-related cytokine TNF-α to induce expression of cytokines/chemokines/adhesion molecules. House dust mite (HDM)-induced allergic asthma and humanized allergic asthma NOD/ SCID murine models were established to assess anti-inflammatory mechanisms in vivo. IL-38 significantly inhibited induced proinflammatory IL-6, IL-1β, CCL5, and CXCL10 production, and antiviral interferon-β and intercellular adhesion molecule-1 expression in the coculture system. Mass cytometry and RNA-sequencing analysis revealed that IL-38 could antagonize the activation of the intracellular STAT1, STAT3, p38 MAPK, ERK1/2, and NF-κB pathways, and upregulate the expression of the host defense-related gene POU2AF1 and anti-allergic response gene RGS13. Intraperitoneal injection of IL-38 into HDM-induced allergic asthma mice could ameliorate airway hyperreactivity by decreasing the accumulation of eosinophils in the lungs and inhibiting the expression of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchoalveolar lavage fluid (BALF) and lung homogenates. Histological examination indicated lung inflammation was alleviated by reductions in cell infiltration and goblet cell hyperplasia, together with reduced Th2, Th17, and innate lymphoid type 2 cell numbers but increased proportions of regulatory T cells in the lungs, spleen, and lymph nodes. IL-38 administration suppressed airway hyperreactivity and asthma-related IL-4 and IL-5 expression in humanized mice, together with significantly decreased CCR3 + eosinophil numbers in the BALF and lungs, and a reduced percentage of human CD4 + CRTH2 + Th2 cells in the lungs and mediastinal lymph nodes. Together, our results demonstrated the anti-inflammatory mechanisms of IL-38 and provided a basis for the development of a regulatory cytokine-based treatment for allergic asthma.

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Hydrodynamic delivery of IL-38 gene alleviates obesity-induced inflammation and insulin resistance

Cited by 26 publications

References 24 publications

Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects

Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma

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