Endogenous sulfur dioxide is a novel adipocyte-derived inflammatory inhibitor.
Endogenous sulfur dioxide is a novel adipocyte-derived inflammatory inhibitor.
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内源性二氧化硫是一种新型脂肪细胞源性炎症抑制剂
DOI：
10.1038/srep27026
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发表时间：
2016-06-01
影响因子：
4.6
通讯作者：
Jin H
中科院分区：
文献类型：
--
作者：
Zhang H;Huang Y;Bu D;Chen S;Tang C;Wang G;Du J;Jin H
本研究旨在确定二氧化硫（SO2）是否可以在脂肪细胞内源性产生，并作为一种新的脂肪细胞衍生的炎症抑制剂。采用荧光高效液相色谱法检测脂肪组织中so2的含量。测定脂肪组织中so2合成酶-天冬氨酸转氨酶（AAT1和AAT2） mRNA和蛋白的表达。体外培养3T3-L1脂肪细胞，用携带AAT1基因的腺病毒或携带AAT1 shRNA的慢病毒感染，然后用肿瘤坏死因子-α (TNF-α)处理。我们发现内源性SO2/AAT通路存在于脂肪组织中，包括血管周围、肾周、附睾、皮下和棕色脂肪组织。AAT1过表达可显著增加so2的产生，抑制TNF-α-诱导的炎症因子、单核细胞趋化蛋白-1 （MCP-1）和白细胞介素-8 （IL-8）的分泌。相反，AAT1敲低可降低so2的产生，并加重TNF-α刺激的MCP-1和IL-8的分泌。机制上，AAT1过表达减弱了TNF-α诱导的i -κB α磷酸化降解和核因子-κB (NF-κB) p65磷酸化，而AAT1敲低则加重了TNF-α激活的NF-κB途径，该途径被SO2阻断。NF-κB抑制剂，PDTC或Bay 11-7082，可消除p65过度磷酸化和AAT1敲低诱导的脂肪细胞炎症。这是首次报道内源性so2是一种新的脂肪细胞衍生的炎症抑制剂。
The present study was designed to determine whether sulfur dioxide (SO2) could be endogenously produced in adipocyte and served as a novel adipocyte-derived inflammatory inhibitor. SO2was detected in adipose tissue using high-performance liquid chromatography with fluorescence detection. SO2synthase aspartate aminotransferase (AAT1 and AAT2) mRNA and protein expressions in adipose tissues were measured. Forin vitrostudy, 3T3-L1 adipocytes were cultured, infected with adenovirus carrying AAT1 gene or lentivirus carrying shRNA to AAT1, and then treated with tumor necrosis factor-α (TNF-α). We found that endogenous SO2/AAT pathway existed in adipose tissues including perivascular, perirenal, epididymal, subcutaneous and brown adipose tissue. AAT1 overexpression significantly increased SO2production and inhibited TNF-α-induced inflammatory factors, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) secretion from 3T3-L1 adipocytes. By contrast, AAT1 knockdown decreased SO2production and exacerbated TNF-α-stimulated MCP-1 and IL-8 secretion. Mechanistically, AAT1 overexpression attenuated TNF-α-induced IκBα phosphorylation and degradation, and nuclear factor-κB (NF-κB) p65 phosphorylation, while AAT1 knockdown aggravated TNF-α-activated NF-κB pathway, which was blocked by SO2. NF-κB inhibitors, PDTC or Bay 11-7082, abolished excessive p65 phosphorylation and adipocyte inflammation induced by AAT1 knockdown. This is the first report to suggest that endogenous SO2is a novel adipocyte-derived inflammatory inhibitor.