Translational Inhibition of Colonic Epithelial Heat Shock Proteins by IFN-γ and TNF-α in Intestinal Inflammation

Hu, Shien; Ciancio, Mae J.; Lahav, Maor; Fujiya, Mikihiro; Lichtenstein, Lev; Anant, Shrikant; Musch, Mark W.; Chang, Eugene B.

doi:10.1053/j.gastro.2007.09.026

Cited by 86 publications

(95 citation statements)

References 34 publications

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“…It is interesting that down-regulation of HSP70 has been found to be associated with IBD development (Bhattacharrya et al 2009;Köken et al 2004;Hu et al 2007). Although we also reported that a 1% GTPs diet aggravated colitis in DSSexposed mice , it was not clear whether 1% GTPs affected the expression HSP70 in that model.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the expressions of HSP70 and HSP27 were found to be down-regulated in actively inflamed mucosa from individuals with IBD (Bhattacharrya et al 2009;Köken et al 2004). It is worth noting that the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin, were also found to be increased in IBD, while it down-regulated HSP70 by targeting its translation stage (Hu et al 2007). The above background suggests that inflammatory signaling molecules aggravate colitis by down-regulating HSPs, thereby disrupting intestinal homeostasis.…”

mentioning

confidence: 99%

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High-dose green tea polyphenols induce nephrotoxicity in dextran sulfate sodium-induced colitis mice by down-regulation of antioxidant enzymes and heat-shock protein expressions

Inoue

Akiyama

Maeda‐Yamamoto

et al. 2011

Cell Stress and Chaperones

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Previously, we reported that oral feeding of 1% green tea polyphenols (GTPs) aggravated the dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, we assessed the toxicity of 1% GTPs in several organs from normal and DSS-exposed mice. Sixty-two male ICR mice were initially divided into four groups. Nontreated group (group 1, n=15) was given standard diet and water, GTPs (group 2, n=15) received 1% GTPs in diet and water, DSS (group 3, n=15) received diet and 5% DSS in water, and GTPs + DSS group (group 4, n=17) received 1% GTPs in diet and 5% DSS in water. We found that group 4 significantly increased (P<0.05) kidney weight, the levels of serum creatinine and thiobarbituric acid-reactive substances in both kidney and liver, as compared with those in group 3. The mRNA expression levels of antioxidant enzymes and heat-shock proteins (HSPs) in group 4 were lower than those of group 3. For instance, heme oxygenase-1 (HO-1), HSP27, and 90 mRNA in the kidney of group 4 were dramatically down-regulated as compared with those of group 3. Furthermore, 1% GTPs diet decreased the expression of HO-1, NAD(P)H:quinone oxidoreductase 1 (NQO1) and HSP90 in kidney and liver of non-treated mice. Taken together, our results indicate that high-dose GTPs diet disrupts kidney functions through the reduction of antioxidant enzymes and heat-shock protein expressions in not only colitis but also non-treated ICR mice.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

High-dose green tea polyphenols induce nephrotoxicity in dextran sulfate sodium-induced colitis mice by down-regulation of antioxidant enzymes and heat-shock protein expressions

Inoue

Akiyama

Maeda‐Yamamoto

et al. 2011

Cell Stress and Chaperones

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“…Specific repression of translation of HSP mRNAs has been described in other contexts; for example under basal conditions, translation of chicken reticulocyte HSP70 mRNA is restricted through a reduced elongation rate (Theodorakis et al 1988). In addition, injection of IFN-γ and TNF-α, inflammatory factors that are also associated with H. pylori infection, were found to preferentially inhibit HSP translation without altering mRNA levels in a mouse model of colitis (Hu et al 2007). Whether H. pylori infection plays a role in specific HSP repression via a mechanism similar to the previously mentioned contexts remains to be seen.…”

Section: Discussionmentioning

confidence: 87%

The Helicobacter pylori cytotoxin CagA is essential for suppressing host heat shock protein expression

Lang

Gorrell

Tafreshi

et al. 2016

Cell Stress and Chaperones

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Bacterial infections typically elicit a strong Heat Shock Response (HSR) in host cells. However, the gastric pathogen Helicobacter pylori has the unique ability to repress this response, the mechanism of which has yet to be elucidated. This study sought to characterize the underlying mechanisms by which H. pylori down-modulates host HSP expression upon infection. Examination of isogenic mutant strains of H. pylori defective in components of the type IV secretion system (T4SS), identified the secretion substrate, CagA, to be essential for down-modulation of the HSPs HSPH1 (HSP105), HSPA1A (HSP72), and HSPD1 (HSP60) upon infection of the AGS gastric adenocarcinoma cell line. Ectopic expression of CagA by transient transfection was insufficient to repress HSP expression in AGS or HEK293T cells, suggesting that additional H. pylori factors are required for HSP repression. RT-qPCR analysis of HSP gene expression in AGS cells infected with wild-type H. pylori or isogenic cagA-deletion mutant found no significant change to account for reduced HSP levels. In summary, this study identified CagA to be an essential bacterial factor for H. pylori-mediated suppression of host HSP expression. The novel finding that HSPH1 is down-modulated by H. pylori further highlights the unique ability of H. pylori to repress the HSR within host cells. Elucidation of the mechanism by which H. pylori achieves HSP repression may prove to be beneficial in the identification of novel mechanisms to inhibit the HSR pathway and provide further insight into the interactions between H. pylori and the host gastric epithelium.

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“…In an animal model of colitis, injection of interferon and TNF-α activated PKR, and resulted in markedly impaired Hsp25 and Hsp70 protein synthesis at the translational level; Hsp25 and Hsp70 were in fact nearly absent in the gut mucosa, while the mRNA of these proteins remained unaffected. The authors observed that the cytokines blocked Hsp70 synthesis twice as much as they blocked β-actin, suggesting that while there is a global reduction in protein translation, Hsp70 is blocked more aggressively (Hu et al 2007). In the case of NDV, however, reduction in protein translation was more global, and not specific to Hsps.…”

Section: Herpes Simplex Virusmentioning

confidence: 99%

Loss of stress response as a consequence of viral infection: implications for disease and therapy

Hooper

Hightower

Hooper

2012

Cell Stress and Chaperones

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Translational Inhibition of Colonic Epithelial Heat Shock Proteins by IFN-γ and TNF-α in Intestinal Inflammation

Cited by 86 publications

References 34 publications

High-dose green tea polyphenols induce nephrotoxicity in dextran sulfate sodium-induced colitis mice by down-regulation of antioxidant enzymes and heat-shock protein expressions

High-dose green tea polyphenols induce nephrotoxicity in dextran sulfate sodium-induced colitis mice by down-regulation of antioxidant enzymes and heat-shock protein expressions

The Helicobacter pylori cytotoxin CagA is essential for suppressing host heat shock protein expression

Loss of stress response as a consequence of viral infection: implications for disease and therapy

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