RESUMO
Heme oxygenase-1 (HO-1) has potent anti-inflammatory activity and recognized vascular protective effects. We have recently described the expression and vascular protective effects of an anti-inflammatory interleukin (IL-19), in vascular smooth muscle cells (VSMC) and injured arteries. The objective of this study was to link the anti-inflammatory effects of IL-19 with HO-1 expression in resident vascular cells. IL-19 induced HO-1 mRNA and protein in cultured human VSMC, as assayed by quantitative RT-PCR, immunoblot, and ELISA. IL-19 does not induce HO-1 mRNA or protein in human endothelial cells. IL-19 activates STAT3 in VSMC, and IL-19-induced HO-1 expression is significantly reduced by transfection of VSMC with STAT3 siRNA or mutation of the consensus STAT binding site in the HO-1 promoter. IL-19 treatment can significantly reduce ROS-induced apoptosis, as assayed by Annexin V flow cytometry. IL-19 significantly reduced ROS concentrations in cultured VSMC. The IL-19-induced reduction in ROS concentration is attenuated when HO-1 is reduced by siRNA, indicating that the IL-19-driven decrease in ROS is mediated by HO-1 expression. IL-19 reduces vascular ROS in vivo in mice treated with TNFα. This points to IL-19 as a potential therapeutic for vascular inflammatory diseases and a link for two previously unassociated protective processes: Th2 cytokine-induced anti-inflammation and ROS reduction.
Assuntos
Regulação Enzimológica da Expressão Gênica/fisiologia , Heme Oxigenase-1/biossíntese , Interleucinas/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Células Cultivadas , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/imunologia , Humanos , Interleucinas/genética , Interleucinas/imunologia , Camundongos , Músculo Liso Vascular/imunologia , Miócitos de Músculo Liso/imunologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Espécies Reativas de Oxigênio/imunologia , Elementos de Resposta/fisiologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Fator de Transcrição STAT3/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Vasculite/genética , Vasculite/imunologia , Vasculite/metabolismoRESUMO
BACKGROUND: Previous work had shown the ability of an aqueous leaf and stem extract of Cissus quandrangularis (300 mg of CQR, CQR-300) to improve components of metabolic syndrome (MS) in overweight individuals. OBJECTIVE: This small pilot study aimed to confirm the efficacy of CQR-300 in reducing the percentage body fat measured using two different methods-bioelectrical impedance assay versus dual-energy X-ray absorptiometry (DEXA). DESIGN: The study was an 8-week double-blind, placebo-controlled pilot trial on 67 individuals who were requested by a dietary counselor to maintain their normal exercise and dietary routines. Participants were randomly divided into two groups, placebo (32 participants) and the CQR-300 group (35 participants), and received 300 mg of corn starch or CQR-300 daily. METHODS: Body fat was measured by bioelectrical impedance using a TANITA impedance meter and by DEXA, with blood samples taken at baseline and at 8 weeks for the measurement of lipid parameters. RESULTS: After 8 weeks of treatment, participants of the placebo group showed a 1.05% decrease in body fat as determined by bioelectrical impedance analysis, but no difference using DEXA. In the same time period, the CQR-300 group had an 8.9% and 12.8% decreases in the body fat as measured by impedance and DEXA, respectively. These values were significantly (p < 0.05) lower than the placebo. Compared with the placebo, the CQR-300 group demonstrated significant (p < 0.05) decreases in the waist and hip circumferences, systolic and diastolic blood pressures, total cholesterol, triglycerides, fasting blood glucose, as well as leptin levels. On the contrary, there were significant (p < 0.05) increases in HDL-cholesterol and adiponectin levels. CONCLUSION: CQR-300 administered as a single 300 mg dose daily was effective in reducing body fat as well as improving blood parameters associated with MS.