The Heat Shock Response Inhibits Inducible Nitric Oxide Synthase Gene Expression by Blocking Iκ-B Degradation and NF-κB Nuclear Translocation

Wong, Hector R.; Ryan, Marnie A.; Wispé, Jonathan R.

doi:10.1006/bbrc.1997.6076

Cited by 106 publications

(61 citation statements)

References 26 publications

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“…We found that blocking of NF-B activation by prior HSP induction was secondary to the stabilization of I B␣. These observations, in which induction of the HSPs blocked nuclear translocation of NF-B by inhibiting I B␣ degradation, are in accord with previous studies (22,23).…”

Section: Discussionsupporting

confidence: 93%

“…Actually, it is well documented that HSP induction inhibits pro-inflammatory cytokine gene expression in mononuclear cells (20,21). Recently, RANTES and inducible NO synthase gene expressions were shown to be inhibited by prior HSP induction in human and murine lung epithelial cells, respectively (22,23). In addition to these in vitro studies, the protective effect of HSP induction was documented to be related to the attenuation of plasma IL-1␤ concentrations in an in vivo model of ALI (14).…”

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confidence: 99%

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Anti-Inflammatory Effect of Heat Shock Protein Induction Is Related to Stabilization of IκBα Through Preventing IκB Kinase Activation in Respiratory Epithelial Cells

Yoo

Lee

et al. 2000

The Journal of Immunology

246

171

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Heat shock protein (HSP) induction confers protection against diverse forms of cellular and tissue injury. However, the mechanism by which HSP exerts cytoprotective effects is unclear. Because HSP induction inhibits genetic expression of pro-inflammatory cytokines, the transcription of which is dependent on NF-κB activation, we explored the relationship between the anti-inflammatory effect of HSP induction and the NF-κB/IκBα pathway. Both HS and sodium arsenite treatment increased HSP70 expression time dependently at mRNA and protein levels. Prior induction of HSP suppressed cytokine-induced IL-8 and TNF-α expression at both mRNA and protein levels. Although HSP induction did not affect total cellular expression of NF-κB, TNF-α-induced increase in NF-κB-DNA binding activity and nuclear translocation of the p65 subunit of NF-κB were inhibited by prior HSP induction, suggesting that activation of NF-κB was blocked. Cytokine-induced IκBα phosphorylation and its degradation were blocked in HSP-induced cells. Immune complex kinase assays demonstrated that TNF-α induced increase in IκB kinase activity was suppressed by prior HSP induction. These results suggest that the anti-inflammatory effect of HSP induction in respiratory epithelial cells is related to stabilization of IκBα, possibly through the prevention of IκB kinase activation, which thereby inhibits activation of NF-κB.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Anti-Inflammatory Effect of Heat Shock Protein Induction Is Related to Stabilization of IκBα Through Preventing IκB Kinase Activation in Respiratory Epithelial Cells

Yoo

Lee

et al. 2000

The Journal of Immunology

246

171

View full text Add to dashboard Cite

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“…Specifically, heat shock inhibits the activation of I B kinase (IKK) activity that normally occurs in response to proinflammatory stimuli (17,121), leading to decreases in phosphorylation (17,121) and subsequent ubiquination (95) of I B␣. The net effect is an inhibition of the degradation of I B␣ that normally occurs after exposure to proinflammatory stimuli (17,93,95,112,121), which prevents NF-B translocation to the nucleus by maintaining it in an inactive, bound state in the cytoplasm. This mechanism functions in the presence of inhibitors of protein synthesis (17) and does not require increased expression of IKK (121).…”

Section: Changes In Expression Of Other Genes As a Results Of Heat Stressmentioning

confidence: 99%

Invited Review: Effects of heat and cold stress on mammalian gene expression

Sonna

Fujita

Gaffin

et al. 2002

Journal of Applied Physiology

539

409

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This review examines the effects of thermal stress on gene expression, with special emphasis on changes in the expression of genes other than heat shock proteins (HSPs). There are ∼50 genes not traditionally considered to be HSPs that have been shown, by conventional techniques, to change expression as a result of heat stress, and there are <20 genes (including HSPs) that have been shown to be affected by cold. These numbers will likely become much larger as gene chip array and proteomic technologies are applied to the study of the cell stress response. Several mechanisms have been identified by which gene expression may be altered by heat and cold stress. The similarities and differences between the cellular responses to heat and cold may yield key insights into how cells, and by extension tissues and organisms, survive and adapt to stress.

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“…This cascade activates HSF-1 in the cytoplasm, which leads to an increase in HSP72 mRNA transcription in the nucleus (1). HSP72 is released back into the cytosol, where it forms a complex with NF-B and I B, inhibiting nuclear translocation of NF-B (11) and stabilizing I B (88).…”

Section: Discussionmentioning

confidence: 99%

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Selkirk¹,

McLellan²,

Wright³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Selkirk GA, McLellan TM, Wright HE, Rhind SG. Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals. Am J Physiol Regul Integr Comp Physiol 296: R575-R586, 2009. First published January 21, 2009 doi:10.1152/ajpregu.90683.2008.-This study examined intracellular cytokine, heat shock protein (HSP) 72, and cellular apoptosis in classic and inflammatory CD14 ϩ monocyte subsets during exertional heat stress (EHS). Subjects were divided into endurance-trained [TR; n ϭ 12, peak aerobic power (V O2peak) ϭ 70 Ϯ 2 ml⅐ kg lean body mass (LBM) Ϫ1 ⅐ min Ϫ1 ] and sedentary-untrained (UT; n ϭ 11, V O2peak ϭ 50 Ϯ 1 ml⅐ kg LBM Ϫ1 ⅐ min Ϫ1 ) groups before walking at 4.5 km/h with 2% elevation in a climatic chamber (40°C, 30% relative humidity) wearing protective clothing until exhaustion (Exh). Venous blood samples at baseline and 0.5°C rectal temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0°C/Exh) were analyzed for cytokines (TNF-␣, IL-1␤, IL-6, IL-1ra, and IL-10) in CD14 ϩϩ CD16 Ϫ /CD14 ϩ CD16 ϩ and HSP72/apoptosis in CD14 Bri / CD14 Dim subsets. In addition, serum levels of extracellular (e)HSP72 were also examined. Baseline and Exh samples were separately stimulated with LPS (1 g/ml) or heat shocked (42°C) and cultured in vitro for 2 h. A greater temperature-dependent increase in CD14 ϩ CD16 ϩ cells was observed in TR compared with UT subjects as well as a greater LPS tolerance following in vitro LPS stimulation. TNF-␣ and IL-1␤ cytokine expression was elevated in CD14 ϩ CD16 ϩ but not in CD14 ϩϩ CD16 Ϫ cells. A greater induction of intracellular HSP72 and eHSP72 was observed in TR compared with UT subjects, which coincided with reduced apoptosis at Exh and following in vitro heat shock. Induced HSP in vitro was not uniform across CD14 ϩ subsets. Findings suggest that circulating CD14 ϩ CD16 ϩ , but not CD14 ϩϩ CD16 Ϫ monocytes, contribute to the proinflammatory cytokine profiles observed during EHS. In addition, the enhanced HSP72 response in endurance-trained individuals may confer improved heat tolerance through both anti-inflammatory and anti-apoptotic mechanisms. immune function; cardiovascular/thermoregulatory strain; flow cytometry; heat shock protein PERIPHERAL BLOOD MONOCYTES play an important role in protection against invading pathogens and activation of innate immunity (46). Based on differential expression of antigenic markers CD14 [part of the LPS receptor, CD14/Toll-like receptor (TLR-4)/MD-2] and CD16 (Fc␥RIII), monocytes can be divided into two phenotypically and functionally distinct subsets (82, 90). The bulk of monocytes are defined as classic monocytes and are strongly positive for surface receptor CD14 (CD14 ϩϩ CD16 Ϫ ), whereas the minor subset are referred to as inflammatory monocytes (CD14 ϩ CD16 ϩ ) because of their high capacity to express proinflammatory cytokines such as TNF-␣ (6, 62, 64, 90). Inflammatory monocytes have the ability to respond directly with antimicrobial activity, whereas the clas...

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The Heat Shock Response Inhibits Inducible Nitric Oxide Synthase Gene Expression by Blocking Iκ-B Degradation and NF-κB Nuclear Translocation

Cited by 106 publications

References 26 publications

Anti-Inflammatory Effect of Heat Shock Protein Induction Is Related to Stabilization of IκBα Through Preventing IκB Kinase Activation in Respiratory Epithelial Cells

Anti-Inflammatory Effect of Heat Shock Protein Induction Is Related to Stabilization of IκBα Through Preventing IκB Kinase Activation in Respiratory Epithelial Cells

Invited Review: Effects of heat and cold stress on mammalian gene expression

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

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