Liu Yongliang, Wang Xinmei, Zhao Yan, Zhao Peiqing, Wang Lianqing, Zhai Qiaoli, Zhang Xiaowei, Tian Wenxiu, Xiang Xinxin, Li Tao
Central of Translation Medicine, Zibo Central Hospital Affiliated to Shandong University, Zibo 255036, China.
Department of Pathology, Zibo Central Hospital Affiliated to Shandong University, Zibo 255036, China.
J Diabetes Res. 2017;2017:4802319. doi: 10.1155/2017/4802319. Epub 2017 May 24.
Tumor necrosis factor--induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a negative regulator of natural and adaptive immunity. The role of TIPE2 in type 2 diabetes mellitus (T2DM) remains unknown, although TIPE2 plays key roles in preserving inflammatory homeostasis.
TIPE2 expression was measured by Western blotting and real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs) isolated from T2DM patients and healthy controls, and tumor necrosis factor- (TNF-), high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and other related biometabolic parameters were detected using a nephelometer or by ELISA. Differentiated THP-1 cells were exposed to siTIPE2 and TIPE2 adenovirus.
TIPE2 was significantly increased in PBMCs from T2DM patients compared with those from healthy controls and was negatively correlated with serum TNF-, IL-6, and hsCRP concentrations but positively correlated with HbA1c and LDL-C in T2DM patients. High glucose treatment (50 mmol/L) can upregulate the expression of TIPE2 and cytokine secretion in differentiated THP-1 cells. siTIPE2 infection exacerbated the increased TNF- and IL-6 concentrations in differentiated THP-1 cells under high glucose conditions (50 mmol/L), while infection with TIPE2 adenovirus reversed the increased TNF- concentration.
The present study indicates that TIPE2 may participate in T2DM by regulating TNF- production.
肿瘤坏死因子诱导蛋白8样2（TIPE2或TNFAIP8L2）是天然免疫和适应性免疫的负调节因子。尽管TIPE2在维持炎症稳态中起关键作用，但其在2型糖尿病（T2DM）中的作用仍不清楚。
采用蛋白质免疫印迹法和实时聚合酶链反应（RT-PCR）检测T2DM患者和健康对照者外周血单个核细胞（PBMC）中TIPE2的表达，并使用散射比浊法或酶联免疫吸附测定法检测肿瘤坏死因子-α（TNF-α）、高敏C反应蛋白（hsCRP）、白细胞介素6（IL-6）及其他相关生物代谢参数。将分化的THP-1细胞分别用TIPE2小干扰RNA（siTIPE2）和TIPE2腺病毒处理。
与健康对照者相比，T2DM患者PBMC中TIPE2显著升高，且与T2DM患者血清TNF-α、IL-6和hsCRP浓度呈负相关，但与糖化血红蛋白（HbA1c）和低密度脂蛋白胆固醇（LDL-C）呈正相关。高糖处理（50 mmol/L）可上调分化的THP-1细胞中TIPE2的表达及细胞因子分泌。在高糖条件（50 mmol/L）下，siTIPE2感染加剧了分化的THP-1细胞中TNF-α和IL-6浓度的升高，而TIPE2腺病毒感染则逆转了TNF-α浓度的升高。
本研究表明，TIPE2可能通过调节TNF-α的产生参与T2DM的发生发展。
