内脏脂肪组织中IL- 36γ的增加是结肠癌中肥胖驱动炎症的关键媒介。

IF 4.8 3区 医学 Q1 GENETICS & HEREDITY
Gema Frühbeck, Sofía Criado, Javier Gómez-Ambrosi, Beatriz Ramírez, Sara Becerril, Amaia Rodríguez, Gabriela Neira, Laura Salmón-Gómez, Víctor Valentí, Rafael Moncada, Jorge Baixauli, Camilo Silva, Victoria Catalán
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引用次数: 0

摘要

肥胖背景下功能失调的脂肪组织(AT)促进慢性炎症状态,与更糟糕的癌症进展和预后相关。白细胞介素(IL)-36γ是肥胖中增加的促炎因子。目的是分析IL-36γ在肥胖患者结肠癌(CC)发展中的作用。从74名志愿者中获得的样本(27名体重正常(NW), 47名肥胖(OB))用于病例对照研究。参与者也根据CC的存在进行细分(45名无CC, 29名有CC)。用促炎因子、脂肪细胞条件培养基(ACM)和IL-36γ处理HT-29细胞,以评估炎症和细胞外基质(ECM)重塑相关分子的表达水平。发现OB和CC患者内脏AT中IL36G和IL36R基因表达水平升高。此外,IL36G的mRNA水平与其受体及AT炎症相关基因(ASC、IL1B和NLRP6)的基因表达水平显著相关。与此一致的是,缺氧、炎症相关因子(LPS、TNF-α和瘦素)以及肥胖患者HT-29癌细胞中的脂肪细胞分泌组上调了IL36G的表达。此外,我们发现IL-36γ增加了HT-29细胞中炎症相关基因(IL36G、il1a、IL1B、IL6、IL8和NGAL)以及ECM标志物(MMP9、SPP1和TNC)的基因表达水平。OB和CC患者VAT中IL36G基因表达水平的增加可能促进有利于肿瘤进展和迁移的促炎微环境。关键信息:肥胖和结肠癌增加内脏脂肪组织中IL36G和IL36R的基因表达水平。肥胖患者的缺氧、炎症相关因素和脂肪细胞分泌组上调HT-29癌细胞中IL36G的mRNA水平。IL-36γ增加HT-29细胞中炎症相关基因(IL36G、IL1A、IL1B、IL6、IL8和NGAL)以及ECM标志物(MMP9、SPP1和TNC)的基因表达水平。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Increased IL- 36γ in visceral adipose tissue as a key mediator of obesity-driven inflammation in colon cancer.

Dysfunctional adipose tissue (AT) in the context of obesity promotes a chronic inflammatory state, associated with worse cancer progression and prognosis. Interleukin (IL)-36γ is a proinflammatory factor increased in obesity. The aim was to analyse the role of IL-36γ in colon cancer (CC) development in patients with obesity. Samples obtained from 74 volunteers (27 with normal weight (NW) and 47 with obesity (OB)) were used in a case-control study. Participants were also subclassified according to the presence of CC (45 without and 29 with CC). HT-29 cells were treated with pro-inflammatory factors, adipocyte conditioned media (ACM) and IL-36γ to evaluate the expression levels of inflammation- and extracellular matrix (ECM) remodelling-related molecules. Increased gene expression levels of IL36G and IL36R in visceral AT from patients with OB and CC were found. Moreover, mRNA levels of IL36G were significantly associated with the gene expression levels of its receptor and relevant genes involved in AT inflammation (ASC, IL1B and NLRP6). Consistently, IL36G expression was upregulated by hypoxia, inflammation-related factors (LPS, TNF-α and leptin) and by the adipocyte secretome from patients with obesity in HT-29 cancer cells. Furthermore, we revealed that IL-36γ increased the gene expression levels of inflammation-related genes (IL36G, IL1 A, IL1B, IL6, IL8 and NGAL) as well as ECM markers (MMP9, SPP1 and TNC) in HT-29 cells. Increased gene expression levels of IL36G in VAT from patients with OB and CC may promote a pro-inflammatory microenvironment favourable for tumour progression and migration. KEY MESSAGES: Obesity and colon cancer increase gene expression levels of IL36G and IL36R in visceral adipose tissue. Hypoxia, inflammation-related factors and the adipocyte secretome from patients with obesity upregulate mRNA levels of IL36G in HT-29 cancer cells. IL-36γ increase the gene expression levels of inflammation-related genes (IL36G, IL1A, IL1B, IL6, IL8 and NGAL) as well as ECM markers (MMP9, SPP1 and TNC) in HT-29 cells.

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来源期刊
Journal of Molecular Medicine-Jmm
Journal of Molecular Medicine-Jmm 医学-医学:研究与实验
CiteScore
9.30
自引率
0.00%
发文量
100
审稿时长
1.3 months
期刊介绍: The Journal of Molecular Medicine publishes original research articles and review articles that range from basic findings in mechanisms of disease pathogenesis to therapy. The focus includes all human diseases, including but not limited to: Aging, angiogenesis, autoimmune diseases as well as other inflammatory diseases, cancer, cardiovascular diseases, development and differentiation, endocrinology, gastrointestinal diseases and hepatology, genetics and epigenetics, hematology, hypoxia research, immunology, infectious diseases, metabolic disorders, neuroscience of diseases, -omics based disease research, regenerative medicine, and stem cell research. Studies solely based on cell lines will not be considered. Studies that are based on model organisms will be considered as long as they are directly relevant to human disease.
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