Role of NF-κB-dependent Caveolin-1 Expression in the Mechanism of Increased Endothelial Permeability Induced by Lipopolysaccharide

Tiruppathì, Chinnaswamy; Shimizu, Jun; Miyawaki-Shimizu, Kayo; Vogel, Stephen M.; Bair, Angela M.; Minshall, Richard D.; Predescu, Dan; Malik, Asrar B.

doi:10.1074/jbc.m703153200

Cited by 96 publications

(84 citation statements)

References 36 publications

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“…In support of our findings, it has been shown that p65 nuclear translocation can be prevented by E 2 in VECs, macrophages, and breast cancer cells (Hsu et al 2000, Ghisletti et al 2005, Tiruppathi et al 2008. Currently, little is known about the NFkB transport machinery.…”

Section: Discussionsupporting

confidence: 76%

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

Jiang¹,

Xu²,

Zheng³

et al. 2010

Journal of Molecular Endocrinology

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Atherosclerosis is an inflammatory disease where lipopolysaccharide (LPS) triggers the release of inflammatory cytokines that accelerate its initiation and progression. Estrogen has been proven to be vasoprotective against atherosclerosis; however, the anti-inflammatory function of estrogen in the vascular system remains obscure. In this study, we investigated the effect of estrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1; listed as CCL2 in the MGI database) production in vascular smooth muscle cells (VSMCs). LPS significantly enhances MCP-1 production and this is dependent on nuclear factor k B (NFkB) signaling, since the use of NFkB inhibitor pyrrolidine dithiocarbamate or the silencing of NFkB subunit p65 expression with specific siRNA largely impairs LPS-enhanced MCP-1 production. On the contrary, 17b-estradiol (E 2 ) inhibits LPS-induced MCP-1 production in a time-and dosedependent manner, which is related to the suppression of p65 translocation to nucleus. Furthermore, p38 MAPK is rapidly activated in response to LPS, while E 2 markedly inhibits p38 MAPK activation. Transfection with p38 MAPK siRNA or the use of p38 MAPK inhibitor SB203580 markedly attenuates LPS-stimulated p65 translocation to nucleus and MCP-1 production, suggesting that E 2 suppresses NFkB signaling by the inactivation of p38 MAPK signaling. LPS promotes VSMCs migration and this is abrogated by MCP-1 antibody, implying that MCP-1 may play a major role as an autocrine factor in atherosclerosis. In addition, E 2 inhibits LPS-promoted cell migration by downregulation of MCP-1 production.Overall, our results demonstrate that E 2 exerts anti-inflammatory property antagonistic to LPS in VSMCs by reducing MCP-1 production, and this effect is related to the inhibition of p38 MAPK/NFkB cascade.

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Section: Discussionsupporting

confidence: 76%

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

Jiang¹,

Xu²,

Zheng³

et al. 2010

Journal of Molecular Endocrinology

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“…Ca 2+ oscillations are known to alter inflammatory cytokine expression by differentially activating transcription factors including NFAT and NF-κB (29). The central role of NF-κB in LPS signaling is well established (54,55). However, our study reveals an alternate inflammatory pathway that requires STIM1-dependent NFAT activity in ECs ( Figure 5).…”

Section: Store-operated Camentioning

confidence: 41%

Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation

Gandhirajan¹,

Meng²,

et al. 2013

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During sepsis, acute lung injury (ALI) results from activation of innate immune cells and endothelial cells by endotoxins, leading to systemic inflammation through proinflammatory cytokine overproduction, oxidative stress, and intracellular Ca 2+ overload. Despite considerable investigation, the underlying molecular mechanism(s) leading to LPS-induced ALI remain elusive. To determine whether stromal interaction molecule 1-dependent (STIM1-dependent) signaling drives endothelial dysfunction in response to LPS, we investigated oxidative and STIM1 signaling of EC-specific Stim1-knockout mice. Here we report that LPSmediated Ca 2+ oscillations are ablated in ECs deficient in Nox2, Stim1, and type II inositol triphosphate receptor (Itpr2). LPS-induced nuclear factor of activated T cells (NFAT) nuclear accumulation was abrogated by either antioxidant supplementation or Ca 2+ chelation. Moreover, ECs lacking either Nox2 or Stim1 failed to trigger store-operated Ca 2+ entry (SOCe) and NFAT nuclear accumulation. LPS-induced vascular permeability changes were reduced in EC-specific Stim1 -/-mice, despite elevation of systemic cytokine levels. Additionally, inhibition of STIM1 signaling prevented receptor-interacting protein 3-dependent (RIP3-dependent) EC death. Remarkably, BTP2, a small-molecule calcium release-activated calcium (CRAC) channel blocker administered after insult, halted LPS-induced vascular leakage and pulmonary edema. These results indicate that ROS-driven Ca 2+ signaling promotes vascular barrier dysfunction and that the SOCe machinery may provide crucial therapeutic targets to limit sepsis-induced ALI.

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“…38 Accordingly, in this study we clearly show that just after METH exposure the transcellular permeability mediated by NF-κB is increased. Also, Tiruppathi et al 39 showed that NF-κB signaling was involved in LPS-increased caveolae-mediated transendothelial albumin permeability. Besides this transcellular permeability, METH also interfered with the paracellular pathway.…”

Section: Discussionmentioning

confidence: 99%

The TNF-α/Nf-κB Signaling Pathway has a Key Role in Methamphetamine–Induced Blood–Brain Barrier Dysfunction

Coelho-Santos

Leitão

Cardoso

et al. 2015

J Cereb Blood Flow Metab

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Methamphetamine (METH) is a psychostimulant that causes neurologic and psychiatric abnormalities. Recent studies have suggested that its neurotoxicity may also result from its ability to compromise the blood-brain barrier (BBB). Herein, we show that METH rapidly increased the vesicular transport across endothelial cells (ECs), followed by an increase of paracellular transport. Moreover, METH triggered the release of tumor necrosis factor-alpha (TNF-α), and the blockade of this cytokine or the inhibition of nuclear factor-kappa B (NF-κB) pathway prevented endothelial dysfunction. Since astrocytes have a crucial role in modulating BBB function, we further showed that conditioned medium obtained from astrocytes previously exposed to METH had a negative impact on barrier properties also via TNF-α/NF-κB pathway. Animal studies corroborated the in vitro results. Overall, we show that METH directly interferes with EC properties or indirectly via astrocytes through the release of TNF-α and subsequent activation of NF-κB pathway culminating in barrier dysfunction.

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Role of NF-κB-dependent Caveolin-1 Expression in the Mechanism of Increased Endothelial Permeability Induced by Lipopolysaccharide

Cited by 96 publications

References 36 publications

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation

The TNF-α/Nf-κB Signaling Pathway has a Key Role in Methamphetamine–Induced Blood–Brain Barrier Dysfunction

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