29 research outputs found

    FoxO1 Links Insulin Resistance to Proinflammatory Cytokine IL-1β Production in Macrophages

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    © 2009 by the American Diabetes Association.[Objetives]: Macrophages play an important role in the pathogenesis of insulin resistance via the production of proinflammatory cytokines. Our goal is to decipher the molecular linkage between proinflammatory cytokine production and insulin resistance in macrophages.[Research design and methods]: We determined cytokine profiles in cultured macrophages and identified interleukin (IL)-1 gene as a potential target of FoxO1, a key transcription factor that mediates insulin action on gene expression. We studied the mechanism by which FoxO1 mediates insulin-dependent regulation of IL-1 expression in cultured macrophages and correlated FoxO1 activity in peritoneal macrophages with IL-1 production profiles in mice with low-grade inflammation or insulin resistance.[Results]: FoxO1 selectively promoted IL-1 production in cultured macrophages. This effect correlated with the ability of FoxO1 to bind and enhance IL-1 promoter activity. Mutations of the FoxO1 binding site within the IL-1 promoter abolished FoxO1 induction of IL-1 expression. Macrophages from insulinresistant obese db/db mice or lipopolysaccharide-inflicted mice were associated with increased FoxO1 production, correlating with elevated levels of IL-1 mRNA in macrophages and IL-1 protein in plasma. In nonstimulated macrophages, FoxO1 remained inert with benign effects on IL-1 expression. In response to inflammatory stimuli, FoxO1 activity was augmented because of an impaired ability of insulin to phosphorylate FoxO1 and promote its nuclear exclusion. This effect along with nuclear factor-B acted to stimulate IL-1 production in activated macrophages.[Conclusions]: FoxO1 signaling through nuclear factor-B plays an important role in coupling proinflammatory cytokine production to insulin resistance in obesity and diabetesThis study was supported in part by American Diabetes Association and National Health Institute Grant DK-066301. No potential conflicts of interest relevant to this article were reported.Peer reviewe

    Chikungunya Disease: Infection-Associated Markers from the Acute to the Chronic Phase of Arbovirus-Induced Arthralgia

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    At the end of 2005, an outbreak of fever associated with joint pain occurred in La Réunion. The causal agent, chikungunya virus (CHIKV), has been known for 50 years and could thus be readily identified. This arbovirus is present worldwide, particularly in India, but also in Europe, with new variants returning to Africa. In humans, it causes a disease characterized by a typical acute infection, sometimes followed by persistent arthralgia and myalgia lasting months or years. Investigations in the La Réunion cohort and studies in a macaque model of chikungunya implicated monocytes-macrophages in viral persistence. In this Review, we consider the relationship between CHIKV and the immune response and discuss predictive factors for chronic arthralgia and myalgia by providing an overview of current knowledge on chikungunya pathogenesis. Comparisons of data from animal models of the acute and chronic phases of infection, and data from clinical series, provide information about the mechanisms of CHIKV infection–associated inflammation, viral persistence in monocytes-macrophages, and their link to chronic signs

    Biology of Bemisia tabaci (Genn.) B biotype (Hemiptera, Aleyrodidae) on tomato genotypes Biologia de Bemisia tabaci (Genn.) Biótipo B (Hemiptera, Aleyrodidae) em genótipos de tomateiro

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    Brazil is one of the main tomato (Solanum lycopersicum) producers worldwide. Nevertheless, considerable part of the production is lost due to Bemisia tabaci (Genn.) B biotype attacks. Resistant plants can be an important method for controlling this pest in an integrated pest management. Tests for evaluating some biological aspects of B. tabaci were carried out on 18 tomato genotypes, in controlled laboratory greenhouse conditions. Thirty-day-old plants placed in plastic cages were infested with 20 whitefly pairs each, for 24 h. The development of at least 30 eggs in three leaflets per plant (repetition) was observed until adult emergence. The development period of insects grown in LA1335, PI365928 and LA722 genotypes took three days longer when compared to the ones grown in PI134418 (20.3 days). The highest mortality rate of whitefly nymphs occurred in PI365928, LA1335 and LA722 genotypes (63.8, 54.5 and 53.3%, respectively), and the smallest ones in IAC294 and IAC68F-22-2 genotypes (4.9 e 6.2%, respectively). LA1335, PI365928 and LA722 genotypes presented moderate feeding nonpreference and/or antibiosis-based resistance to B. tabaci B biotype.<br>O Brasil é um dos maiores produtores mundiais de tomate (Solanum lycopersicum), porém grande parte da produção é perdida devido ao ataque de Bemisia tabaci (Genn.) biótipo B. Entre as táticas de controle dessa praga num manejo integrado de pragas, pode-se relacionar a resistência de plantas. Ensaios para avaliar alguns aspectos biológicos de B. tabaci foram realizados com 18 genótipos de tomateiro, em condições controladas de laboratório (casa de vegetação). Plantas com 30 dias de idade foram colocadas em gaiolas plásticas e infestadas com 20 casais de moscas-brancas cada, durante 24h. Acompanhou-se então o desenvolvimento de pelo menos 30 ovos em três folíolos por planta (repetição) até a emergência dos insetos. Os insetos criados nos genótipos LA1335, PI365928 e LA722 apresentaram prolongamento de três dias no período de desenvolvimento, em relação aos criados em PI134418 (20,3 dias). As maiores taxas de mortalidade das ninfas de mosca-branca ocorreram nos genótipos PI365928, LA1335 e LA722 (63,8, 54,5 e 53,3%, respectivamente) e as menores, nos genótipos IAC294 e IAC68F-22-2 (4,9 e 6,2%, respectivamente). Os genótipos LA1335, PI365928 e LA722 apresentam resistência moderada do tipo não-preferência para alimentação e/ou antibiose a B. tabaci biótipo B
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