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

Abstract

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.

<p>Impact of Low Interferon-γ and IL-10 Levels on TNF-α and IL-6 Production by PHA-Induced PBMCs in Type 2 Diabetes Mellitus</p>

“…These findings contradict the conventional notion that proinflammatory cytokines such as TNF-α and IL-6 contribute to insulin resistance. [16][17][18] Figure 1 Ratios of (A) TNF-α/IFN-γ and (B) IL-6/IFN-γ in 3-day PHA-induced PBMC cultures in the control and T2DM groups. PHA, phytohemagglutinin; T2DM, type 2 diabetes mellitus; PBMCs; peripheral blood mononuclear cells; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; IFN-γ, interferon-γ.…”

Apelin‑13 ameliorates metabolic and cardiovascular disorders in a rat model of type 2 diabetes with a high‑fat diet

“…A previous study indicated that high levels of TNF-α is a crucial risk factor for diabetes (37). Furthermore, TNF-α is an important indicator of insulin resistance in obesity and may serve as a target for improving obesity-induced insulin resistance in patients with type 2 diabetes (38). Leptin, first discovered by Zhang et al in 1994, is a hormone that is secreted from adipose tissues and circulates in the blood (39,40).…”

Metabolomics Monitoring of Treatment Response to Brain Tumor Immunotherapy

“…In other studies, mostly in in vitro or murine experiments, found that exposure to tumor cells cause TAMs to shift to glycolysis with a more immunosuppressive phenotype. These TAMs secrete lactate, TNF and IL6 (48)(49)(50). Moreover, the canonical markers of M1 or M2 activation can be co-expressed by TAMs (43), explaining the conflicting studies on TAM metabolism within the TME.…”