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| The regulatory role of IL-33 in metabolic diseases. IL-33/ST2 axis regulates metabolic diseases through: (1) promoting AAM polarization; (2) regulating the differentiation and functions of Treg and Th2; and (3) regulating the function of ILC2.

| The regulatory role of IL-33 in metabolic diseases. IL-33/ST2 axis regulates metabolic diseases through: (1) promoting AAM polarization; (2) regulating the differentiation and functions of Treg and Th2; and (3) regulating the function of ILC2.

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As a cytokine in interleukin-1(IL-1) family, interleukin-33(IL-33) usually exists in the cytoplasm and cell nucleus. When the cells are activated or damaged, IL-33 can be secreted into extracellular and regulate the functions of various immune cells through binding to its specific receptor suppression of tumorigenicity 2 (ST2). Except regulating th...

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... to the vital role of IL-33 in the metabolic homeostasis, a sound understanding of the production, regulation, and function of IL-33 will facilitate the treatment of metabolic disorders. The potential mechanisms (Figure 1) of IL-33/ST2 axis in the metabolic disorders may include: (1) IL-33 promotes the AAM polarization; (2) IL-33 regulates Tregs and Th2 differentiation and function; and (3) IL-33 regulates the function of ILC2. Notably, the AAM polarization induced by IL-33 depends on Type 2 cytokines, which may be released from ILC2. ...

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... Moreover, IL-33 also plays an important role in immune regulation. It can regulate Tregs and Th2 differentiation and function and stimulate immune cells such as dendritic cells, macrophages and mast cells to produce inflammatory cytokines (24,26,27). In this study, IHC staining of IL-33 in human EAC tissues showed that IL-33 was mainly expressed in the cytoplasm in EAC and in the nucleus in adjacent normal epithelial cells. ...
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Background: The progression from chronic gastroesophageal reflux disease (GERD) to Barrett esophagus (BE) and esophageal adenocarcinoma (EAC) is an inflammatory-driven neoplastic change. Interleukin-33 (IL-33) has identified as a crucial factor in several inflammatory disorders and malignancies. Methods: The high-density tissue microarray of the human EAC was analyzed with IL-33 immunohistochemistry staining (IHC). By anastomosing the jejunum with the esophagus, the rat model of EAC with mixed gastroduodenal reflux was established. The expression of IL-33 was determined using quantitative real-time polymerase chain reaction (RT-qPCR), western blot (WB), IHC and enzyme-linked immunosorbent assay (ELISA). Esophageal adenocarcinoma cells (OE19 and OE33) and human esophageal epithelial cells (HEECs) were used. Results: In the cytoplasm of human EAC tissue, IL-33 expression was substantially greater than in adjacent normal tissue. In rat model, the expression of IL-33 in the EAC group was considerably greater than in the control group, and this expression increased with the upgrade of pathological stage. In in vitro experiment, the mRNA and protein levels of IL-33 were considerably greater in OE19 and OE33 than in HEECs. The stimulation of IL-33 enhanced the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of OE19 and OE33, but soluble ST2 (sST2) inhibited these effects. IL-33 stimulated the release of IL-6 by OE19 and OE33 cells. Conclusion: This study demonstrated the overexpression of IL-33 in the transition from GERD to EAC and that IL-33 promoted carcinogenesis in EAC cells through ST2. IL-33 might be a possible preventive target for EAC.
... The PW with MS and higher levels of circulating IL-15 showed also higher levels of IL-1b, IL-5, IL-6, IL-10, IL-13, and IL-33. Higher levels of these cytokines are also thought to contribute (positively or negatively) to RI [7,14,27,28]. Even when these cytokines were considered in the statistical model, higher The most interesting finding is that PW with MS and higher levels of circulating IL-15 showed improved IR when compared with those with MS but a lower level of circulating IL-15. ...
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... Importantly, IL-33, a newly identified member of the IL-1 cytokine family, plays a protective role against inflammation of adipose tissue by directly and indirectly regulating T-regulatory cells (Tregs) function. Further investigations are required to determine to which extent IL-33 contributes to metabolic disorders in humans [16]. ...
... Our study found that IL-33 mRNA expression was significantly decreased in all MetS groups compared with that in healthy controls, and this decrease was higher with the increase in MetS criteria (diabetic and hypertensive groups were lower than obese and dyslipidemia groups). Previous studies investigated the link between IL-33, an anti-inflammatory cytokine, and obesity [16]. IL-33 has a crucial role in lipid metabolism and exhibits a protective role in the pathogenesis of atherosclerosis and acute cardiovascular events [53]. ...
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... Our study found that IL-33 mRNA expression was significantly decreased in all MetS groups compared with that in healthy controls, and this decrease was higher with the increase in MetS criteria (diabetic and hypertensive groups were lower than obese and dyslipidemia groups). Previous studies investigated the link between IL-33, an anti-inflammatory cytokine, and obesity [16]. IL-33 has a crucial role in lipid metabolism and exhibits a protective role in the pathogenesis of atherosclerosis and acute cardiovascular events [53]. ...
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... In addition, IL-33 promotes the beiging of white adipocytes and energy expenditure by activating group 2 innate lymphoid cells (ILC2s) in adipose tissue, contracting obesity and its related disorders [14][15][16]. Despite the beneficial effects as an anti-inflammatory factor [9][10][11]17], the double-edged sword effect of IL-33 in immunity and metabolism has gained growing attention [10,11,18]. Meanwhile, studies have also reported that IL-33 may play an undetermined role in obesity and its cardiovascular or diabetic complications since the specific role of IL-33 in the pathogenesis and development of several metabolic diseases seems to be inconsistent [9,[14][15][16][17]. ...
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... IL-33, a cytokine related to IL-1, has a role both in inflammation, and in metabolism (135,136). IL-33 binds to receptor, ST2. Levels of IL-33 are reduced in ALS, and levels of soluble ST2 are increased in ALS (84). ...
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