The changes of plasma myostatin levels in patients with type 2 diabetes mellitus (T2D) and their clinical correlation were investigated. We recruited 43 T2D patients and 20 age-matched healthy subjects. Plasma myostatin, lipid and glucose, and serum insulin were determined. T2D patients showed significantly higher fasting plasma glucose (FPG), serum insulin and triglyceride levels, and lower high-density lipoprotein levels than normal control subjects (P<0.01). Mean plasma myostatin level in T2D patients and health controls was (66.5±17.8) and (46.2±13.8) ng/mL, respectively. An unpaired t test showed that the increase of myostatin in the T2D patients was significant (P<0.001). In both healthy control and T2D groups, the female subjects showed higher myostatin levels than the male subjects. In the T2D patients, plasma level of myostatin was negatively correlated with body mass index (BMI, r=-0.42, P<0.01) and FPG (r=-0.51, P[Symbol: see text]0.01), but positively correlated with insulin resistance index (HOMA-IR, r=0.48, P<0.01). Up-regulation of plasma myostatin in the T2D patients and its correlation with BMI, FPG and blood insulin sensitivity suggests that plasma myostatin may be implicated in the pathogenesis of T2D and thus presented as a therapeutic target for treating the disease. Furthermore, circulating myostatin levels may be used as a biomarker for the disease.
In the past, the clinical therapy for autoimmune diseases, such as autoimmune polychondritis ear disease, was mostly limited to nonspecific immunosuppressive agents, which could lead to variable responses. Currently, gene therapy aims at achieving higher specificity and less adverse effects. This concept utilizes the adoptive transfer of autologous T cells that have been retrovirally transduced ex vivo to express and deliver immunoregulatory gene products to sites of autoimmune inflammation. In the animal model of collagen-induced autoimmune polychondritis ear disease (CIAPED), the adoptive transfer of IL-12p40-expressing collagen type II (CII)-specific CD4+ T-cell hybridomas resulted in a significantly lower disease incidence and severity compared with untreated or vector-only-treated animals. In vivo cell detection using bioluminescent labels showed that transferred CII-reactive T-cell hybridomas accumulated in the inflamed earlobes of the mice with CIAPED. In vitro analysis demonstrated that IL-12p40-transduced T cells did not affect antigen-specific T-cell activation or systemic anti-CII Ab responses. However, IL-12p40-transduced T cells suppressed IFN-γ and augmented IL-4 production, indicating their potential to act therapeutically by interrupting Th1-mediated inflammatory responses via augmenting Th2 responses. These results indicate that the local delivery of IL-12p40 by T cells could inhibit CIAPED by suppressing autoimmune responses at the site of inflammation.
Clinical therapy of autoimmune diseases used to be limited to non-specific immune-suppressive agents and was, for the most part, based on chance observations. Currently, gene therapy research aims at achieving higher specificity and thus less adverse side effects. This concept comprises the adoptive transfer of autologous T-cells that have been retrovirally transduced ex vivo to express and deliver immune-regulatory gene products to sites of autoimmune inflammation. In the animal model of collagen-induced autoimmune polychondritis ear disease (CIAPED), the adoptive transfer of IL-12p40 expressing collagen type II (CII)-specific CD4+ T-cell hybridomas resulted in a significantly lower disease incidence and severity compared with untreated or vector-only treated animals. In vivo cell detection using bioluminescent labels showed that transferred CII-reactive T-cell hybridomas accumulated in inflamed ear lobes in mice with CIAPED. In vitro analysis demonstrated that IL-12p40-transduced T-cells did not affect the antigen-specific T-cell activation or systemic anti-CII antibody responses. However, IL-12p40-transduced T-cells suppressed IFN-γ and augmented IL-4 production, indicating its potential to act therapeutically by interrupting Th1-mediated inflammatory responses via augmenting Th2 responses. These results indicate that the local delivery of IL-12p40 by T-cells could inhibit CIAPED by suppressing autoimmune responses at the site of inflammation.
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