TNF-alpha modulates statin effects on secretion and expression of MCP-1, PAI-1 and adiponectin in 3T3-L1 differentiated adipocytes

dc.contributor.authorLobo, Sylvia Madeira de Vergueiro [UNIFESP]
dc.contributor.authorQuinto, Beata Marie [UNIFESP]
dc.contributor.authorOyama, Lila Missae [UNIFESP]
dc.contributor.authorNakamichi, Renata [UNIFESP]
dc.contributor.authorRibeiro, Artur Beltrame [UNIFESP]
dc.contributor.authorZanella, Maria Tereza [UNIFESP]
dc.contributor.authorDalboni, Maria Aparecida [UNIFESP]
dc.contributor.authorBatista, Marcelo Costa [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionHosp Israelita Albert Einstein
dc.contributor.institutionTufts Univ
dc.description.abstractPurpose: Systemic inflammatory conditions, as seen in obesity and in the metabolic syndrome, are associated with high plasmatic levels of proatherogenic and prothromboticadipokines and low levels of adiponectin. Inhibitors of HMG-CoA reductase have beneficial effects in reducing cardiovascular events attributed predominantly to its lipid-lowering effects and recent studies suggest that these effects might be due to its anti-inflammatory properties. Based on the pleiotropic properties of simvastatin we studied the effects of this drug on the secretion and expression of adiponectin, PAI-1 and MCP-1 in mature adipocytes under baseline conditions and after an inflammatory stimulation.Materials and methods: the differentiated adipocytes were incubated with 10 mu M simvastatin or vehicle and TNF-alpha 10 ng/mL or vehicle were added to treatment media. After 24 h of incubation, the media was harvested and the proteins of interest were analyzed by Multiplex method. Gene expression was analyzed by real time-PCR.Results: the addition of TNF-alpha increased the expression and secretion of MCP-1 and PAI-1. However, stimulation did not interfere with the secretion of adiponectin, despite having significantly reduced its expression. Our data also demonstrated that simvastatin reduced the expression and secretion of MCP-1, under baseline (770.4 +/- 199.9 vs 312.7 +/- 113.7 and 1.00 +/- 0.14 vs 0.63 +/- 0.13, p <0.05, respectively) and inflammatory conditions (14945 +/- 228.7 vs 7837.6 +/- 847.4 and 24.16 +/- 5.49 vs 14.97 +/- 2.67, p < 0.05, p < 0.05, respectively). Simvastatin also attenuated the increase in expression and secretion of PAI-1 induced by TNF-alpha (16898.6 +/- 1663.3 vs 12922.1 +/- 843.9 and 5.19 +/- 3.12 vs 0.59 +/- 0.16, respectively p < 0.05), but under baseline conditions had no effect on the expression or secretion of PAI-1. the statin increased the expression of adiponectin under baseline conditions and inflammatory stimulation (1.03 +/- 0.08 vs 4.0 +/- 0.96 and 0.77 +/- 0.19 vs 2.16 +/- 0.23, respectively, p < 0.05) and also increased the secretion of this adipokine. but only with the inflammatory stimulus (5347.7 1789.3 vs 7327.3 +/- 753.6, p <0.05).Conclusions: Our findings suggested that simvastatin counteracted the stimulatory effect of TNF-alpha on secretion and expression of MCP-1, PAI-1 and adiponectin, implying a potential anti-atherogenic effect during the inflammatory process; these pleitropic effects were more pronounced with HMG-CoA reductase inhibitor. (C) 2012 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.affiliationHosp Israelita Albert Einstein, Intens Care Ctr, Dialysis Unit, São Paulo, Brazil
dc.description.affiliationTufts Univ, Sch Med, Div Nephrol, Boston, MA 02111 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: FAPESP: 07/51483-0
dc.identifier.citationCytokine. London: Academic Press Ltd- Elsevier B.V., v. 60, n. 1, p. 150-156, 2012.
dc.publisherElsevier B.V.
dc.rightsAcesso aberto
dc.titleTNF-alpha modulates statin effects on secretion and expression of MCP-1, PAI-1 and adiponectin in 3T3-L1 differentiated adipocytesen
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