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

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

Author Lobo, Sylvia Madeira de Vergueiro Autor UNIFESP Google Scholar
Quinto, Beata Marie Autor UNIFESP Google Scholar
Oyama, Lila Missae Autor UNIFESP Google Scholar
Nakamichi, Renata Autor UNIFESP Google Scholar
Ribeiro, Artur Beltrame Autor UNIFESP Google Scholar
Zanella, Maria Tereza Autor UNIFESP Google Scholar
Dalboni, Maria Aparecida Autor UNIFESP Google Scholar
Batista, Marcelo Costa Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Hosp Israelita Albert Einstein
Tufts Univ
Abstract Purpose: 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.
Keywords Simvastatin
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: FAPESP: 07/51483-0
Date 2012-10-01
Published in Cytokine. London: Academic Press Ltd- Elsevier B.V., v. 60, n. 1, p. 150-156, 2012.
ISSN 1043-4666 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 150-156
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000310095000025

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