Activation of PPARγ enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes

Rampino, Teresa; Guidetti, Cristina; Gregorini, Marilena; Soccio, Grazia; Marasà, Maddalena; Libetta, Carmelo; Guida, Gianenrico; Amici, Mara De; Canton, Antonio Dal

doi:10.1016/j.trim.2007.03.003

Cited by 8 publications

(6 citation statements)

References 36 publications

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“…However, the role of Pcgf4 and Ybx1 in nephrotoxicity has not yet been fully evaluated. It has been shown that Il-2 is down-regulated in Cisplatin and Cyclosporine nephrotoxicity [51,52]. Consistent with these studies, we found Il-2 as a common hub gene in Cisplatin, Lead acetate and Cyclosporine nephrotoxicity.…”

Section: Discussionsupporting

confidence: 91%

Molecular Mechanisms Underlying the Nephrotoxicity of Cisplatin, Lead Acetate and Cyclosporine: Key Roles of Myc and Smad4

Askari¹,

Abdullahi²,

Poortahmasebi³

et al. 2017

Biol syst Open Access

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It is well documented that use of Cisplatin, Lead acetate and Cyclosporine in the chemotherapy and medical interventions is highly associated with nephrotoxicity and interrelated comorbidities. Here, we proposed the possible molecular mechanisms responsible for nephrotoxicity of these compounds. We utilized the microarray dataset GSE59913 consisting of approximately 600 different compounds profiled in up to 8 different tissues. After analysis with GEO2R, gene expression profiles of three aforementioned compounds were integrated with protein-protein interactions (PPI) networks and topological properties of the networks were measured using Cytoscape software. We found several key genes and signaling pathways that seem to be involved in nephrotoxicity of the examined compounds. Myc and Smad4 were identified as principal players of three compounds' nephrotoxicity through various pathways. Our results revealed the critical functions of Il2, Jak-Stat, Mapk-Pi3k, TGFβ and Ca 2+ signaling pathways as well as novel biomarkers that may mediate the nephrotoxicity of Cisplatin, Lead acetate and Cyclosporine. The significantly altered genes in the compound-treated samples were substantially correlated with regulation of cell proliferation, apoptosis, inflammatory responses and homeostatic processes. This study reveals the important hub genes, biological networks and key pathways as well as novel biomarkers involved in nephrotoxicity of Cisplatin, Lead acetate and Cyclosporine.

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Section: Discussionsupporting

confidence: 91%

Molecular Mechanisms Underlying the Nephrotoxicity of Cisplatin, Lead Acetate and Cyclosporine: Key Roles of Myc and Smad4

Askari¹,

Abdullahi²,

Poortahmasebi³

et al. 2017

Biol syst Open Access

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“…Apparently, the amelioration of the CSA-evoked lipid peroxidation, oxidative stress, and dyslipidemia contributes to the inhibitory effect of pioglitazone on the CSA-evoked hypertension. The clinical importance of this research is warranted particularly in view of recent information that the activation of PPARγ boosts the immunosuppressant effect of CSA via the inhibition of T cell proliferation and IL-2 release [43]. Interestingly, the combined use of PPARγ ligands and low-dose CSA might represent a rationale therapeutic approach for the prevention of CSA nephrotoxicity while maintaining adequate immunosuppression [43,44].…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone abrogates cyclosporine-evoked hypertension via rectifying abnormalities in vascular endothelial function

El‐Mas

El‐Gowelli

Abd-Elrahman

et al. 2011

Biochemical Pharmacology

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In addition to insulin sensitization, the thiazolidenedione drug pioglitazone exhibits favorable circulatory effects. Here, we hypothesized that pioglitazone protects against the hypertension and related vascular derangements caused by the immunosuppressant drug cyclosporine (CSA). Compared with vehicle (olive oil)-treated rats, chronic treatment with CSA (20 mg/kg/day s.c., for 14 days) increased blood pressure (BP), reduced the aortic protein expression of phosphorylated eNOS (p-eNOS), and impaired responsiveness of isolated aortas to endothelium-dependent vasorelaxations induced by carbachol. The effects of CSA on BP, aortic p-eNOS, and carbachol relaxations were abolished upon concurrent administration of pioglitazone (2.5 mg/kg/day). Serum levels of adiponectin, an adipose tissue-derived adipokine, were not altered by CSA but showed significant elevations in rats treated with pioglitazone or pioglitazone plus CSA. The possibility that alterations in the antioxidant and/or lipid profile contributed to the CSA-pioglitazone BP interaction was investigated. Pioglitazone abrogated the oxidative (aortic superoxide dismutase), lipid peroxidation (aortic malondialdyde), and dyslipidemic (serum LDL levels and LDL/HDL ratio) effects of CSA. Histologically, CSA caused focal disruption in the endothelial lining of the aorta and this effect disappeared in rats co-treated with pioglitazone. Collectively, pioglitazone abrogates the hypertensive effect of CSA via ameliorating detrimental changes in vascular endothelial NOS/NO pathway and oxidative and lipid profiles caused by CSA.

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“…In adipocytes, PPARg activates the expression of a variety of beneficial cell factors such as resistin, IL-6, and TNFα (Sharma and Staels, 2007;Qin et al, 2008), as well as plays multiple roles in glucose and lipid metabolism, atherosclerosis, and inflammatory responses (Tontonoz et al, 1995;Li et al, 2000;Fernyhough et al, 2007;Széles et al, 2007;Rampino et al, 2007). PPARg is involved in the regulation of the expression of lipid metabolism-related genes, which can promote adipocyte differentiation, and a number of protein factor genes secreted by adipocytes, such as lipoprotein lipase, the fatty acid binding protein, acetyl CoA synthetase, and glucose transporter 4.…”

Section: Discussionmentioning

confidence: 99%

Long-term effects of evodiamine on expressions of lipogenesis and lipolysis genes in mouse adipose and liver tissues

Jiang¹,

Li²,

Yang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Evodiamine, the major alkaloid component isolated from the fruit of dried, unripened Evodia rutaecarpa Bentham, affects the plasma levels of cholecystokinin and various biological events such as gastric emptying and gastrointestinal transit; these effects of evodiamine were previously investigated in male rats. In this study, we aimed to investigate the effects of evodiamine on average daily weight gain, rectal temperature, and expressions of genes involved in lipid metabolism in liver and adipose tissues. Evodiamine was added as a supplement, comprising 0.02, 0.04, and 0.06% of the diet fed to mice for 1, 2, 3, and 4 weeks. Results showed that average daily weight gain and rectal temperature decreased significantly over time in a dosedependent manner. Evodiamine changed expressions of the peroxisome proliferator-activated receptor-g (PPARg) in mouse adipose and liver tissues in time-and dose-dependent manners. We found that evodiamine Long-term effects of evodiamine on lipid metabolism decreased mRNA expression of the sterol-regulatory element binding protein (SREBP-1c) and fatty acid synthase in adipose tissue. In addition, evodiamine increased expressions of hormone-sensitive lipase in both liver and adipose tissues. Interestingly, evodiamine increased the expression of triglyceride hydrolase only in adipose tissue. In conclusion, evodiamine could influence lipid metabolism through regulation of the expressions of its key genes, as well as reduce body heat and body weight.

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Activation of PPARγ enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes

Cited by 8 publications

References 36 publications

Molecular Mechanisms Underlying the Nephrotoxicity of Cisplatin, Lead Acetate and Cyclosporine: Key Roles of Myc and Smad4

Molecular Mechanisms Underlying the Nephrotoxicity of Cisplatin, Lead Acetate and Cyclosporine: Key Roles of Myc and Smad4

Pioglitazone abrogates cyclosporine-evoked hypertension via rectifying abnormalities in vascular endothelial function

Long-term effects of evodiamine on expressions of lipogenesis and lipolysis genes in mouse adipose and liver tissues

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