Stress response decreases NF-kappaB nuclear translocation and increases I-kappaBalpha expression in A549 cells.

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

doi:10.1172/jci119425

Cited by 141 publications

(126 citation statements)

References 24 publications

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“…5B). These slowly migrated bands were confirmed as phosphorylated I B␣ in immunoblotting with Ab specific to phosphorylated I B␣ at Ser 32 (Fig. 5C).…”

Section: Hsp Induction Stabilizes I B␣ By Blocking I B␣ Phosphorylationmentioning

confidence: 72%

“…TNF-␣ leads to sequential activation of the downstream NF-B-inducing kinase (NIK) and recently isolated TNF-␣-inducible I B kinase complex (IKK␣ and IKK␤, also known as IKK-1 and IKK-2, respectively) (7)(8)(9)(10)(11). Upon cell stimulation by a wide variety of stimuli, signal-responsive IKK␣ and -␤ are activated and directly phosphorylate Ser 32 and Ser 36 in the I B␣, triggering ubiquitination at Lys 21 and Lys 22 , and rapid degradation of I B␣ in 26S proteasome (4 -6). This process liberates NF-B, allowing it to translocate to the nucleus.…”

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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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“…5B). These slowly migrated bands were confirmed as phosphorylated I B␣ in immunoblotting with Ab specific to phosphorylated I B␣ at Ser 32 (Fig. 5C).…”

Section: Hsp Induction Stabilizes I B␣ By Blocking I B␣ Phosphorylationmentioning

confidence: 72%

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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“…HSPs may prevent NF-B activation by either inhibiting I B degradation, inducing I B expression, or both. 28 The experiments performed here do not allow discrimination between these two possibilities. However, NF-B activation during reperfusion seems to be independent of I B degradation as shown by us 24 and others.…”

Section: Discussionmentioning

confidence: 83%

The atrial natriuretic peptide and cGMP: Novel activators of the heat shock response in rat livers

Kiemer¹,

Gerbes²,

Bilzer³

et al. 2002

Hepatology

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Preischemic treatment with atrial natriuretic peptide (ANP) attenuates ischemia-reperfusion injury of the rat liver via cyclic guanosine monophosphate (cGMP). The attenuated activation of nuclear factor B (NF-B) seems to contribute to this effect. The aim of this study was to determine whether heat shock proteins are involved in these molecular pathways. Livers of male Sprague-Dawley rats were continuously perfused with Krebs-Henseleit (KH) buffer with or without ANP or 8-Br-cGMP. In different experiments livers were perfused with or without ANP for 20 minutes, kept in cold storage solution for 24 hours, and reperfused. Activation of heat shock transcription factor (HSF) (by electrophoretic mobility shift assay), heat shock protein 70 (HSP70), and glyceraldehyde phosphate dehydrogenase T he "heat shock response" is elicited by a variety of stimuli, including thermal, chemical, and physical stress, as well as short-term ischemia. All organisms respond to such detrimental environmental factors by induction of a group of protective proteins termed heat shock proteins (HSP) (see elsewhere for reviews 1-4 ). The HSPs are subdivided into multimember families based on the molecular weights of the proteins encoded (HSP90, HSP70, HSP60, and the small HSP family), of which HSP70 is one of the most extensively studied in mammalian cells. 2 Studies have revealed that HSPs, in particular HSP70, not only confer thermotolerance, but also protect against oxygen radical toxicity and seem to play an important role in the protection against ischemia reperfusion injury (IRPI). 3,4 Both ischemic 5 or heat shock preconditioning 6-8 induce HSP70 in the liver and the induced HSP70 may contribute to the attenuation of IRPI. This is supported by findings that overexpression of HSP70 in transgenic mice increases the resistance of the heart to ischemic injury. 9,10 HSPs are regulated primarily by changes in gene transcription controlled by a transcription factor termed heat shock factor (HSF). 11,12 The activation process of HSF appears to involve HSF oligomerization from a monomeric to a trimeric state and is associated with HSF hyperphosphorylation. 13 Activated HSF binds to a DNA consensus sequence in the HSP70 promotor termed the heat shock element, 14 leading to the transcription of the HSP70 gene.HSPs seem to protect cells by facilitating the folding of nascent proteins and renaturation or refolding of partially denatured or unfolded proteins. 15 In addition, HSPs can also restrict inflammatory response. Several reports have shown the capacity of HSPs to inhibit the translocation of the proinflammatory transcription factor NF-B and the subsequent expression of inflammatory enzymes 16 and cytokines, such as tumor necrosis factor ␣ (TNF-␣). 1,[17][18][19][20][21] Recently we could show that hormonal preconditioning of livers with the atrial natriuretic peptide (ANP) attenuates reperfusion injury after both warm 22 and cold 23 ischemia of rat livers. The hepatoprotective action of this cardiovascular hormone is mediated via its guanylat...

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“…A direct inhibition of iNOS by hydrogen peroxide has also been reported in mesangial cells (Jaimes et al, 1997). Furthermore, prior induction of a stress response has been shown to inhibit nuclear transcription factor B (NF-B)-mediated gene regulation (Wong et al, 1997) and cytokine release (Zahler et al, 2000). Thus, BHinduced production of oxygen free radicals may prevent iNOS gene transcription, possibly through inhibition of protein kinase C membrane translocation (Arese and Schwarzer, 1997), by blocking the interaction of NF-B with its binding site in the 5Ј-flanking region of the iNOS gene.…”

Section: Discussionmentioning

confidence: 87%

Macrophage Preconditioning with Synthetic Malaria Pigment Reduces Cytokine Production via Heme Iron-Dependent Oxidative Stress

Taramelli

Recalcati

Basilico

et al. 2000

Laboratory Investigation

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SUMMARY:Hemozoin (malaria pigment), a polymer of hematin (ferri-protoporphyrin IX) derived from hemoglobin ingested by intraerythrocytic plasmodia, modulates cytokine production by phagocytes. Mouse peritoneal macrophages (PM) fed with synthetic ␤-hematin (BH), structurally identical to native hemozoin, no longer produce tumor necrosis factor ␣ (TNF␣) and nitric oxide (NO) in response to lipopolysaccharide (LPS). Impairment of NO synthesis is due to inhibition of inducible nitric oxide synthase (iNOS) production. BH-mediated inhibition of PM functions cannot be ascribed to iron release from BH because neither prevention by iron chelators nor down-regulation of iron-regulatory protein activity was detected. Inhibition appears to be related to pigment-induced oxidative stress because (a) thiol compounds partially restored PM functions, (b) heme oxygenase (HO-1) and catalase mRNA levels were up-regulated, and (c) free radicals production increased in BH-treated cells. The antioxidant defenses of the cells determine the response to BH: microglia cells, which show a lower extent of induction of HO-1 and catalase mRNAs and lower accumulation of oxygen radicals, are less sensitive to the inhibitory effect of BH on cytokine production. Results indicate that BH is resistant to degradation by HO-1 and that heme-iron mediated oxidative stress may contribute to malaria-induced immunosuppression. This study may help correlate the different clinical manifestations of malaria, ranging from uncomplicated to severe disease, with dysregulation of phagocyte functions and promote better therapeutic strategies to counteract the effects of hemozoin accumulation. (Lab Invest 2000, 80:1781-1788.I ntraerythrocytic stage plasmodia digest hemoglobin in the food vacuole, where the globin is degraded and heme is detoxified, principally by polymerization/crystallization into hemozoin, an insoluble, microcrystalline derivative of ferri-protoporphyrin IX (␣ hematin, AH) (Bohle et al, 1997;Francis et al, 1997;Pagola et al, 2000;Slater et al, 1991). As parasites mature, hemozoin (malaria pigment) accumulates in the food vacuole and remains in the "residual body" after schizont rupture. Pigment is found inside host's phagocytes following ingestion of whole parasites or "residual bodies." Although a clinical correlation between the presence of pigment in circulating neutrophils and monocytes and disease severity is established (Nguyen et al, 1995), the nature of the interaction between pigment and phagocytes, as well as its contribution to the pathogenesis of malaria, and particularly its severe complications, are still controversial. Indeed, both pro-inflammatory (induction of tumor necrosis factor ␣ [TNF␣], interleukin-6 [IL-6], and chemotactic cytokines) (Pichyangkul et al, 1994;Prada et al, 1995;Sherry et al, 1995) and antiinflammatory activities (inhibition of respiratory burst and adhesion molecule expression and of TNF␣ and nitric oxide [NO] production) (Prada et al, 1995;Schwarzer et al, 1992;Taramelli et al, 1995Taramelli et al, , 1998 ha...

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Stress response decreases NF-kappaB nuclear translocation and increases I-kappaBalpha expression in A549 cells.

Cited by 141 publications

References 24 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

The atrial natriuretic peptide and cGMP: Novel activators of the heat shock response in rat livers

Macrophage Preconditioning with Synthetic Malaria Pigment Reduces Cytokine Production via Heme Iron-Dependent Oxidative Stress

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