Heat Shock Protein 70 Confers Cardiovascular Protection During Endotoxemia via Inhibition of Nuclear Factor-κB Activation and Inducible Nitric Oxide Synthase Expression in the Rostral Ventrolateral Medulla

Chan, Julie Y.H.; Ou, Chen-Chun; Ling-lin, Wang; Chan, Samuel H.H.

doi:10.1161/01.cir.0000143082.63063.33

Cited by 81 publications

(99 citation statements)

References 34 publications

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“…It is known that NF-B positively regulates the expression of pro-inflammatory cytokines, including TNF-␣, IL-1␤, and IL-6. Furthermore, it is also known that upregulation of HSP70 expression by heat shock inhibits the inflammatory stimuli-dependent activation of NF-B through various mechanisms (47)(48)(49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

Tanaka

Namba

Arai

et al. 2007

Journal of Biological Chemistry

131

126

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Inflammatory bowel disease (IBD) involves infiltration of leukocytes into intestinal tissue, resulting in intestinal damage induced by reactive oxygen species (ROS). Pro-inflammatory cytokines and cell adhesion molecules (CAMs) play important roles in this infiltration of leukocytes. The roles of heat shock factor 1 (HSF1) and heat shock proteins (HSPs) in the development of IBD are unclear. In this study, we examined the roles of HSF1 and HSPs in an animal model of IBD, dextran sulfate sodium (DSS)-induced colitis. The colitis worsened or was ameliorated in HSF1-null mice or transgenic mice expressing HSP70 (or HSF1), respectively. Administration of DSS up-regulated the expression of HSP70 in colonic tissues in an HSF1-dependent manner. Expression of pro-inflammatory cytokines and CAMs and the level of cell death observed in colonic tissues were increased or decreased in DSS-treated HSF1-null mice or transgenic mice expressing HSP70, respectively, relative to control wild-type mice. Relative to macrophages from control wildtype mice, macrophages prepared from HSF1-null mice or transgenic mice expressing HSP70 displayed enhanced or reduced activity, respectively, for the generation of pro-inflammatory cytokines in response to lipopolysaccharide stimulation. Suppression of HSF1 or HSP70 expression in vitro stimulated lipopolysaccharide-induced up-regulation of CAMs or ROS-induced cell death, respectively. This study provides the first genetic evidence that HSF1 and HSP70 play a role in protecting against DSS-induced colitis. Furthermore, this protective role seems to involve various mechanisms, such as suppression of expression of pro-inflammatory cytokines and CAMs and ROS-induced cell death. Inflammatory bowel disease (IBD),2 Crohn disease, and ulcerative colitis have become substantial health problems with an actual prevalence of 200 -500 cases/100,000 people in western countries, which almost double every 10 years (1). Although the etiology of IBD is not yet fully understood, recent studies suggest that IBD involves chronic inflammatory disorders in the intestine because of "a vicious cycle." Infiltration into intestinal tissues causes intestinal mucosal damage induced by reactive oxygen species (ROS) that are released from the activated leukocytes, and this intestinal mucosal damage further stimulates the infiltration of leukocytes (2). To understand the molecular mechanism underlying the pathogenesis of IBD and to develop new types of clinical drugs for IBD, identification of endogenous factors that positively or negatively affect the development of IBD is important. For this purpose, various experimental animal colitis models, in particular the dextran sulfate sodium (DSS)-and trinitrobenzenesulfonic acid-induced colitis models, have been used (3).Pro-inflammatory cytokines play an important role in the activation and infiltration of leukocytes that are associated with IBD. This conclusion is supported by a range of evidence. Increases in the levels of various pro-inflammatory cytokines (such as tumor necr...

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Section: Discussionmentioning

confidence: 99%

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

Tanaka

Namba

Arai

et al. 2007

Journal of Biological Chemistry

131

126

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“…59 In vivo hyperthermia in mice or rats is frequently done at 42°C for 15 to 20 minutes. 10,60 In addition, cells in culture were frequently exposed to heat throughout rather prolonged time periods, for example up to 6 hours. 6,61 Under these conditions, heat shock proteins were implicated in NF-B inhibition.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Heat Exposure Inhibits Inflammation by Abrogating Recruitment of and Nuclear Factor-κB Activation in Neutrophils Exposed to Chemotactic Cytokines

Choi

Salanova

Rolle

et al. 2008

The American Journal of Pathology

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Cytokines, such as granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-8 attract neutrophils into inflammatory sites. During emigration from the blood neutrophils interact with extracellular matrix proteins such as fibronectin. Fibronectin provides ␤2-integrin co-stimulation, allowing GM-CSF and IL-8 to activate nuclear factor (NF)-B, an effect that does not occur in suspension. We tested the hypothesis that exposure of mice to fever-like temperatures abrogates neutrophil recruitment and NF-B activation in a mouse model of skin inflammation. Mice that were exposed to 40°C for 1 hour showed strongly reduced GM-CSF-and IL-8-induced neutrophilic skin inflammation. In vitro heat exposure did not interfere with neutrophil adhesion or spreading on fibronectin but strongly inhibited migration toward both cytokines. Using specific inhibitors, we found that PI3-K/Akt was pivotal for neutrophil migration and that heat down-regulated this pathway. Furthermore, neutrophils on fibronectin showed abrogated NF-B activation in response to GM-CSF and IL-8 after heat. In vivo heat exposure of mice followed by ex vivo stimulation of isolated bone marrow neutrophils confirmed these results. Finally, less NF-B activation was seen in the inflammatory lesions of mice exposed to fever-like temperatures as demonstrated by in situ hybridization for IB␣ mRNA. These new findings suggest that heat may have anti-inflammatory effects in neutrophil-dependent inflammation. (Am J Pathol

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“…Furthermore, phosphorylation of HSP 27 by p38 leads to association with IKK in HeLa cells upon TNF-α treatment, and suppression of NFκB activity (113). Other heat shock proteins, such as HSP 72, have been shown to bind to both the IκB-α and the p65 subunit of the NFκB complex, inhibiting NFκB activation and downstream production of cytokines and inducible nitric oxide synthase (110,114). The acute and chronic actions of E2 on NFκB and the HSR are summarized in Figure 5.…”

Section: The Stress Response and Nfκb-late Effectsmentioning

confidence: 99%

Estrogen, NFκB, and the Heat Shock Response

Stice

Knowlton

2008

Mol Med

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Estrogen has pleiotropic actions, among which are its anti-apoptotic, anti-inflammatory, and vasodilatory effects. Recently, an interaction between 17β-estradiol (E2) and the transcription factor nuclear factor κB (NFκB) has been identified. NFκB has a central role in the control of genes involved in inflammation, proliferation, and apoptosis. Prolonged activation of NFκB is associated with numerous inflammatory pathological conditions. An important facet of E2 is its ability to modulate activity of NFκB via both genomic and nongenomic actions. E2 can activate NFκB rapidly via nongenomic pathways, increase cellular resistance to injury, and induce expression of the protective class of proteins, heat shock proteins (HSPs). HSPs can bind to many of the pro-apoptotic and pro-inflammatory targets of NFκB and, thus, indirectly inhibit many of its deleterious effects. In addition, HSPs can block NFκB activation and binding directly. Similarly, genomic E2 signaling can inhibit NFκB, but does so through alternative mechanisms. This review focuses on the molecular mechanisms of cross-talk between E2, NFκB, and HSPs, and the biological relevance of this cross-talk.

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Heat Shock Protein 70 Confers Cardiovascular Protection During Endotoxemia via Inhibition of Nuclear Factor-κB Activation and Inducible Nitric Oxide Synthase Expression in the Rostral Ventrolateral Medulla

Cited by 81 publications

References 34 publications

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

Genetic Evidence for a Protective Role for Heat Shock Factor 1 and Heat Shock Protein 70 against Colitis

Short-Term Heat Exposure Inhibits Inflammation by Abrogating Recruitment of and Nuclear Factor-κB Activation in Neutrophils Exposed to Chemotactic Cytokines

Estrogen, NFκB, and the Heat Shock Response

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