NLRP3 inflammasome and visceral adipose tissue

peer reviewedIt is recognized that abdominal obesity is accompanied by a chronic low-grade inflammation that is involved in the pathogenesis of insulin resistance and type 2 diabetes. Metabolic syndrome and type 2 diabetes are associated with an abnormal production of pro-inflammatory cytokines, an increased level of acute-phase proteins and an activation of inflammatory signalling pathways. These pro-inflammatory cytokines, mainly produced by adipose tissue macrophages, are involved in development of obesity-associated insulin resistance and in the progression from obesity to type 2 diabetes. Particularly, the interleukin-1 beta may play a key role through the activation of the NLRP3 inflammasome. Adipose tissue topography, more than the total amount of fat, may play an important pathogenic role. Indeed, the presence of metabolic abnormalities in obesity is associated with a deleterious immunological and inflammatory profile of visceral adipose tissue and with an increased activation of the NLRP3 inflammasome in macrophages infiltrating visceral adipose tissue. Targeting inflammation, especially NLRP3 inflammasome, may offer potential novel therapeutic perspectives in the prevention and treatment of type 2 diabetes

HIV-1 and NF-kappaB activation by photo-oxidative stress

peer reviewe

NF-kappa B activation by reactive oxygen species: Fifteen years later

The transcription factor NF-kappa B plays a major role in coordinating innate and adaptative immunity, cellular proliferation, apoptosis and development. Since the discovery in 1991 that NF-kappa B maybe activated by H(2)o(2), several laboratories have put a considerable effort into dissecting the molecular mechanisms underlying this activation. Whereas early studies revealed an atypical mechanism of activation, leading to I kappa B alpha Y42 phosphorylation independently Of I kappa B kinase (IKK), recent findings suggest that H2O2 activates NF-kappa B mainly through the classical IKK-dependent pathway. The molecular mechanisms leading to IKK activation are, however, cell-type specific and will be presented here. In this review, we also describe the effect of other ROS (HOCl and O-1(2)) and reactive nitrogen species on NF-kappa B activation. Finally, we critically review the recent data highlighting the role of ROS in NF-kappa B activation by proinflammatory cytokines (TNF-alpha and IL-1 beta) and lipopolysaccharide (LPS), two major components of innate immunity. (c) 2006 Elsevier Inc. All rights reserved

Impairment of the mitochondrial electron chain transport prevents NF-kappa B activation by hydrogen peroxide.

A large body of work has been devoted to mechanisms leading to the activation of the transcription factor NF-kappa B in various cell types. Several studies have indicated that NF-kappa B activation by numerous stimuli depends on the intracellular generation of reactive oxygen species (ROS). In this report, we first demonstrated that inhibition of the electron transport chain by either rotenone or antimycine A gave rise to dose-dependent inhibition of NF-kappa B translocation induced by 150 microM of hydrogen peroxide (H2O2). Conversely, the impairment of the mitochondrial respiratory chain did not affect T lymphocyte treatment by TNF-alpha (tumor necrosis factor alpha) or pre-B lymphocyte treatment with LPS (lipopolysaccharide). We also showed that oligomycine which inhibits ATP synthase and FCCP, which uncouples respiration also led to dose-dependent inhibition of NF-kappa B activation by H2O2. All these inhibitors were also shown to inhibit mitochondrial respiration in lymphocytes assessed by oxygen consumption. Although only a transient drop in ATP concentration was observed when lymphocytes were treated by H2O2, this effect was remarkably reinforced in the presence of oligomycine demonstrating the crucial role of ATP in the signal transduction pathway induced by H2O2

Perturbation of actin dynamics induces NF-κB activation in myelomonocytic cells through an NADPH oxidase-dependent pathway

Although several reports showed the effect of compounds disrupting microtubules on NF-κB (nuclear factor κB) activation, nothing is known about agents perturbing actin dynamics. In the present study, we have shown that actin cytoskeleton disruption induced by actin-depolymerizing agents such as cytochalasin D and latrunculin B and actin-polymerizing compounds such as jasplakinolide induced NF-κB activation in myelomonocytic cells. The transduction pathway involved the IκB (inhibitory κB) kinase complex and a degradation of IκBα. We have shown that NF-κB activation in response to the perturbation of actin dynamics required reactive oxygen species, as demonstrated by the effect of antioxidants. Actin cytoskeleton disruption by cytochalasin D induced O(2)(−) release from human monocytes, through the activation of the NADPH oxidase, as confirmed by the phosphorylation and by the membrane translocation of p47(phox). NF-κB activation after actin cytoskeleton disruption could be physiologically relevant during monocyte activation and/or recruitment into injured tissues, where cellular attachment, migration and phagocytosis result in cyclic shifts in cytoskeletal organization and disorganization

identification of new parterns of the NOD2 protein in an invasion model of intestinal epithelial cells by salmonella typhimurium

identification de nouveaux partenaires de la protéine NOD