Upregulation of Tumor Necrosis Factor- α -Induced Protein 8-Like 2 mRNA Is Negatively Correlated with Serum Concentrations of Tumor Necrosis Factor- α and Interleukin 6 in Type 2 Diabetes Mellitus.

BACKGROUND: Tumor necrosis factor- α -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.

METHODS: 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- α (TNF- α ), 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.

RESULTS: TIPE2 was significantly increased in PBMCs from T2DM patients compared with those from healthy controls and was negatively correlated with serum TNF- α , 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- α 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- α concentration.

CONCLUSIONS: The present study indicates that TIPE2 may participate in T2DM by regulating TNF- α production.