Divergent roles of endothelial NF-κB in multiple organ injury and bacterial clearance in mouse models of sepsis

Ye, Xiaobing; Ding, Jianqiang; Zhou, Xiaozhou; Guo-qian, Chen; Liu, Shu Fang

doi:10.1084/jem.20071393

Cited by 170 publications

(118 citation statements)

References 44 publications

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“…A vascular cause of the neurological symptoms in IP is supported by the finding that cell typespecific deletion of Nemo in neurons and glial cells did not lead to any obvious deficits (Fig. 1 B; van Loo et al, 2006), findings for the role of NF-B in the permeability of peripheral endothelial cells (Kisseleva et al, 2006;Ye et al, 2008).…”

Section: Discussionsupporting

confidence: 53%

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

Ridder¹,

Wenzel²,

Müller³

et al. 2015

J Cell Biol

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Section: Discussionsupporting

confidence: 53%

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

Ridder¹,

Wenzel²,

Müller³

et al. 2015

J Cell Biol

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“…Activation of NF-jB results in induction of several inflammatory/oxidative stress responsive genes, leading to an exacerbation of ONS (Baldwin, 1996). Activation of NF-jB has been documented in TBI (Hang et al, 2006;Jin et al, 2008;Ye et al, 2008). Consistent with these findings, we recently observed that FPI to cultured astrocytes resulted in the activation of NF-jB, while inhibition of such activation significantly blocked trauma-induced astrocyte swelling ( Jayakumar et al, in press).…”

Section: Nuclear Factor-kappa Bmentioning

confidence: 54%

“…Several studies have documented that TBI results in the activation of the transcriptional factor nuclear factor-kappa B (NF-jB) ( Hang et al, 2006;Jin et al, 2008;Ye et al, 2008). Additionally, NF-jB has been implicated in brain edema and astrocyte swelling in ammonia toxicity (Sinke et al, 2008).…”

Section: Inhibition Of Nuclear Factor-kappa B Reduces Trauma-induced mentioning

confidence: 99%

Aquaporin-4 Expression in Cultured Astrocytes after Fluid Percussion Injury

Rao

Reddy

Curtis

et al. 2011

Journal of Neurotrauma

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The development of cytotoxic brain edema resulting in increased intracranial pressure is a major cause of death occurring in the early phase of traumatic brain injury (TBI). Such edema predominantly develops as a consequence of astrocyte swelling. We recently documented that fluid percussion injury (FPI) to cultured astrocytes causes cell swelling. Since aquaporin-4 (AQP4) has been strongly implicated in the development of brain edema/astrocyte swelling in various neurological conditions, this study examined the effect of in vitro trauma on AQP4 protein expression in cultured astrocytes. Exposure of astrocytes to FPI resulted in a significant upregulation of AQP4 protein in the plasma membrane due to neosynthesis, as cycloheximide blocked the trauma-induced AQP4 upregulation. Silencing the aqp4 gene by siRNA resulted in a significant reduction in trauma-induced astrocyte swelling, indicating a critical role of AQP4 in this process. We recently documented that oxidative/nitrative stress (ONS), the mitochondrial permeability transition (mPT), and activation of mitogen-activated protein kinases (MAPKs), contribute to trauma-induced astrocyte swelling in culture. We now show that inhibition of these factors reduces the upregulation of AQP4 following trauma. Since TBI has been shown to activate nuclear factor-kappa B (NF-κB), as well as the Na(+),K(+),Cl(-) co-transporter (NKCC), both of which are implicated in brain edema/astrocyte swelling in other conditions, we also examined the effect of BAY 11-7082 and bumetanide, inhibitors of NF-κB and NKCC, respectively, and found that these agents also significantly inhibited the trauma-induced AQP4 upregulation. Our findings show that in vitro trauma upregulates AQP4, and that ONS, MAPKs, mPT, NF-κB, and NKCC are involved in its upregulation.

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“…This was experimentally illustrated in a transgenic mouse model in which a degradation-resistant form I-B␣ was overexpressed in the vascular endothelium, resulting in sequestration of NF-B and effective blunting of the TLR4 signaling cascade (92). The endothelium of these mice expressed lower levels of vascular adhesion molecules after LPS stimulation.…”

Section: The Endotheliummentioning

confidence: 98%

Inflection points in sepsis biology: from local defense to systemic organ injury

Seeley

Matthay

Wolters

2012

American Journal of Physiology-Lung Cellular and Molecular Phys

104

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Sepsis and septic shock lead to considerable morbidity and mortality in developed and developing countries. Despite advances in understanding the innate immune events that lead to septic shock, molecular therapies based on these advances have failed to improve sepsis mortality. The clinical failure of laboratory-derived therapies may be, in part, due to the pleiotropic consequences of the acute inflammatory response, which is the focus of this review. A brisk response to infecting organism is essential for pathogen containment and eradication. However, systemic spread of inflammation beyond a single focus leads to organ injury and higher mortality. The primary goal of this article is to discuss recent animal- and human-based scientific advances in understanding the host response to infection and to highlight how these defense mechanisms can be locally beneficial but systemically detrimental. There are other factors that determine the severity of sepsis that are beyond the scope of this review, including the virulence of the pathogen and regulation by Toll-like receptors. Specifically, this review focuses on how the effector mechanisms of platelets, mast cells, neutrophil extracellular traps (NETs), and the endothelium participate in combating local infections yet can induce organ injury during systemic infection.

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Divergent roles of endothelial NF-κB in multiple organ injury and bacterial clearance in mouse models of sepsis

Cited by 170 publications

References 44 publications

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

Aquaporin-4 Expression in Cultured Astrocytes after Fluid Percussion Injury

Inflection points in sepsis biology: from local defense to systemic organ injury

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