Tobacco smoke cooperates with interleukin‐1β to alter β‐catenin trafficking in vascular endothelium resulting in increased permeability and induction of cyclooxygenase‐2 expression<i>in vitro</i>and<i>in vivo</i>

Barbieri, Silvia Stella; Weksler, Babette B.

doi:10.1096/fj.06-7557com

Cited by 83 publications

(81 citation statements)

References 35 publications

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“…38 Interestingly, AKT-driven cell signaling is altered by CS in other organs. [39][40][41][42] Based on our results, the apoptotic effects of CS in the liver seem to be caspase-independent. Of note, the deleterious effects of CS in the liver were not observed after a short exposure (5 days).…”

Section: Discussionsupporting

confidence: 54%

Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats

et al. 2009

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The prevalence of cigarette smoking (CS) is increased among obese subjects, who are susceptible to develop nonalcoholic fatty liver disease (NAFLD). We investigated the hepatic effects of CS in control and obese rats. Control and obese Zucker rats were divided into smokers and nonsmokers (n ‫؍‬ 12 per group). Smoker rats were exposed to 2 cigarettes/day, 5 days/week for 4 weeks. The effects of CS were assessed by biochemical analysis, hepatic histological examination, immunohistochemistry, and gene expression analysis. Phosphorylation of AKT and extracellular signal-regulated kinase (ERK) and quantification of carbonylated proteins were assessed by western blotting. As expected, obese rats showed hypercholesterolemia, insulin resistance, and histological features of NAFLD. Smoking did not modify the lipidic or glucidic serum profiles. Smoking increased alanine aminotransferase serum levels and the degree of liver injury in obese rats, whereas it only induced minor changes in control rats. Importantly, CS increased the histological severity of NAFLD in obese rats. We also explored the potential mechanisms involved in the deleterious effects of CS. Smoking increased the degree of oxidative stress and hepatocellular apoptosis in obese rats, but not in controls. Similarly, smoking increased the hepatic expression of tissue inhibitor of metalloproteinase-1 and procollagen-alpha2(I) in obese rats, but not in controls. C igarette smoking (CS) is considered a worldwide major cause of preventable morbidity and mortality. 1 The main clinical consequences of prolonged exposure to CS are chronic respiratory diseases, increased incidence of a variety of cancers, and increased risk of atherothrombotic clinical events such as myocardial infarction. 2 Hepatologists have traditionally paid scant attention to the deleterious effects of CS. This reflects the fact that smoking per se does not appear to cause liver injury and therefore is not considered a causative agent for chronic liver diseases. 3 However, there is in-

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Section: Discussionsupporting

confidence: 54%

Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats

et al. 2009

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“…This mechanism has also been reported in LMVECs in response to acrolein-induced lung injury (Jang et al, 2011). Furthermore, IL1b has been shown to act in conjunction with tobacco smoke in mouse cardiac endothelial cells to induce the disassembly of the adherens junction complexes and the subsequent translocation of b-catenin to the nucleus (Barbieri et al, 2008;Barbieri and Weksler, 2007). Although these studies did not directly examine Cldn5 as an affected end point, they led us to explore the spatial regulation of b-catenin during IL-1b-mediated downregulation of Cldn5 in BMVECs.…”

Section: Discussionmentioning

confidence: 59%

Non-muscle Mlck is required for β-catenin- and FoxO1-dependent downregulation of Cldn5 in IL-1β-mediated barrier dysfunction in brain endothelial cells

Beard

Haines

et al. 2014

Journal of Cell Science

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Aberrant elevation in the levels of the pro-inflammatory cytokine interleukin-1b (IL-1b) contributes to neuroinflammatory diseases. Blood-brain barrier (BBB) dysfunction is a hallmark phenotype of neuroinflammation. It is known that IL-1b directly induces BBB hyperpermeability but the mechanisms remain unclear. Claudin-5 (Cldn5) is a tight junction protein found at endothelial cell-cell contacts that are crucial for maintaining brain microvascular endothelial cell (BMVEC) integrity. Transcriptional regulation of Cldn5 has been attributed to the transcription factors b-catenin and forkhead box protein O1 (FoxO1), and the signaling molecules regulating their nuclear translocation. Non-muscle myosin light chain kinase (nmMlck, encoded by the Mylk gene) is a key regulator involved in endothelial hyperpermeability, and IL-1b has been shown to mediate nmMlck-dependent barrier dysfunction in epithelia. Considering these factors, we tested the hypothesis that nmMlck modulates IL-1b-mediated downregulation of Cldn5 in BMVECs in a manner that depends on transcriptional repression mediated by b-catenin and FoxO1. We found that treating BMVECs with IL-1b induced barrier dysfunction concomitantly with the nuclear translocation of b-catenin and FoxO1 and the repression of Cldn5. Most importantly, using primary BMVECs isolated from mice null for nmMlck, we identified that Cldn5 repression caused by b-catenin and FoxO1 in IL-1b-mediated barrier dysfunction was dependent on nmMlck.

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“…This medium was replaced with fresh medium containing 0.5% FBS and TS at a final concentration of 0.03 puffs/ml. Although there is no standardized way to express cigarette smoke extract, this level of TS is similar to concentrations used in other studies examining TS effects on endothelial cells [28][29][30]. EC were incubated for 24 h before characterization of TS effects.…”

Section: Tobacco Smoke Treatment Of Ecmentioning

confidence: 99%

Regulated complement deposition on the surface of human endothelial cells: Effect of tobacco smoke and shear stress

Yin

Ghebrehiwet

Weksler

et al. 2008

Thrombosis Research

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Cigarette smoke and hemodynamic stress both contribute to vascular inflammation and associated atherosclerosis. We recently demonstrated direct activation of complement components C4 and C3 on human endothelial cells (EC). The present study was designed to explore complement activation on bone marrow microvascular endothelial cells (BMEC) and human umbilical vein endothelial cells (HUVEC) in response to endothelial cell injury by tobacco smoke extract, shear stress, or other known inflammatory and atherogenic mediators, lipopolysaccharide (LPS) and INF-γ. Following treatment, confluent EC monolayers were exposed to plasma (60 min, 37 °C), and cell surface deposition of stable complement derivatives C4d, iC3b and SC5b-9 was measured in situ using an ELISA approach. Consistent with previous results, moderate levels of C4d, iC3b and SC5b-9 deposition were observed on native EC monolayers exposed to human plasma. Tobacco smoke and shear stress enhanced EC C4d deposition. In contrast, LPS and INF-γ failed to affect EC mediated complement activation, despite evidence of EC activation illustrated by ICAM-1 expression. The combination of tobacco smoke and shear stress nearly doubled EC C4d expression. No increases in iC3b or SC5b-9 were noted, suggesting inhibition of classical and alternative pathway C3 convertase assembly or activity. Indeed, concomitantly increased surface expression of complement regulatory proteins CD35 (CR1) and CD55 was observed following EC exposure to tobacco smoke and shear stress. These results suggest that a balance between complement activation and regulation exists at the EC surface, and may impact vascular injury leading to thrombosis, arteriosclerosis, and atherogenesis.

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Tobacco smoke cooperates with interleukin‐1β to alter β‐catenin trafficking in vascular endothelium resulting in increased permeability and induction of cyclooxygenase‐2 expressionin vitroandin vivo

Cited by 83 publications

References 35 publications

Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats

Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats

Non-muscle Mlck is required for β-catenin- and FoxO1-dependent downregulation of Cldn5 in IL-1β-mediated barrier dysfunction in brain endothelial cells

Regulated complement deposition on the surface of human endothelial cells: Effect of tobacco smoke and shear stress

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