l-γ-Glutamyl-l-cysteinyl-glycine (glutathione; GSH) and GSH-related enzymes in the regulation of pro- and anti-inflammatory cytokines: a signaling transcriptional scenario for redox(y) immunologic sensor(s)?

Haddad, John J.; Harb, Hisham L.

doi:10.1016/j.molimm.2004.09.029

Cited by 141 publications

(87 citation statements)

References 332 publications

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“…The antiproliferative effects of LXT as the link intracellular oxidative stress was demonstrated in our study. Redox status is important in the regulation of the immune system (17), and GSH homeostasis plays a key role in the treatment of diseases in which cytokines are major participants in the pathophysiology (18). Our findings showing disease-dependent decreases of intracellular GSH concentration in MRL/lpr mice are consistent with literature data Table I.…”

Section: Discussionsupporting

confidence: 91%

Longdan Xiegan Tang has immunomodulatory effects on CD4+CD25+ T cells and attenuates pathological signs in MRL/lpr mice

Lee

Chang²

2010

Int J Mol Med

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Abstract. Longdan Xiegan Tang (LXT) is a Chinese herbal medicine that is prescribed as an anti-inflammatory aid, a hepato-protectant, and an immunostimulant. In this study, we examined the biological effects of LXT administration in MRL/lpr mice. MRL/lpr mice provide a good model of systemic lupus erythematosus (SLE). These mice develop immunological disturbances and dysregulation in Th1 and Th2 cytokine production. Female mice were randomly separated into two groups. The experimental group received LXT (250 mg/kg/day, po) from 19 to 21 weeks of age. Splenic CD3 + CD4 + , CD3 + CD8 + , and CD4 + CD25 + T cells were increased in the LXT-administered mice compared to MRL/lpr controls, and this was associated with splenomegaly. There was a marked reduction in IFN-Á, TNF-·, anti-dsDNA antibody, and there were reduced IgG immune complex deposits in the glomeruli. LXT also restored kidney glutathione levels, thereby limiting the toxic effects of the inflammatory mediators iNOS and COX-2, which are overproduced in MRL/lpr mice. Two-dimensional gel electrophoresis was used to analyze proteome changes. LXT protected MRL/lpr mice against developing the lupus syndrome through upregulation of phosphoglycerate kinase 1 and down-regulation of ferritin light chain 1, selenium-binding protein 2, and ·-enolase. This study indicates that LXT at this dose and time course of administration was effective in reducing oxidative stress associated with disease progression in MRL/lpr mice. LXT could be useful as adjunctive therapy for reducing distress in SLE.

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Section: Discussionsupporting

confidence: 91%

Longdan Xiegan Tang has immunomodulatory effects on CD4+CD25+ T cells and attenuates pathological signs in MRL/lpr mice

Lee

Chang²

2010

Int J Mol Med

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“…Intracellular glutathione homeostasis plays a major role in the maintenance of intracellular redox environment and regulates a number of critical cellular functions (44). One of the initial events in many inflammatory responses is the depletion of intracellular GSH (44).…”

Section: Discussionmentioning

confidence: 99%

“…One of the initial events in many inflammatory responses is the depletion of intracellular GSH (44). Growing evidence suggests that an altered cellular redox has a profound role in inflammation through the activation of various kinases and redox-sensitive transcription factors such as NF-kB rel proteins, which differentially regulate the genes encoding various proinflammatory cytokines (44,45).…”

Section: Discussionmentioning

confidence: 99%

Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy

Alam

Ghousunnissa

Nair

et al. 2010

The Journal of Immunology

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“…The tripeptide L-Á-glutamyl-L-cysteinyl-glycine, or glutathione, a ubiquitous thiol, plays a major role in maintaining cellular redox state and regulating signalling pathways more commonly altered by oxidative stress (1)(2)(3). The reduced glutathione (GSH) and its oxidized form (GSSG) represent the major cellular redox buffer, therefore the ratio GSH/GSSG is a good indicator for the redox environment of the cell.…”

Section: Introductionmentioning

confidence: 99%

Glutathionylation of p65NF-κB correlates with proliferating/apoptotic hepatoma cells exposed to pro- and anti-oxidants

Alisi

Piemonte²,

Pastore³

et al. 2009

Int J Mol Med

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Abstract.Oxidative stress influences a variety of regulatory proteins, including nuclear factor-κB (NF-κB). NF-κB is critical for maintaining the proliferation/apoptosis balance in hepatocytes. In this study we investigated the causal links between glutathione, NF-κB and hepatocyte damage. HepG2 and 3B cells were exposed to different doses of H 2 O 2 or N-acetylcysteine (NAC) and the proliferation/apoptosis rate, glutathione forms, and p65NF-κB glutathionylation and activity were analysed. Our results demonstrate that H 2 O 2 stopped proliferative response at low doses, but induced apoptosis only at high doses. In contrast, NAC exerted, proportionally to its concentration, a dual role simultaneously increasing both proliferation and apoptosis. Interestingly, the levels of proteinbound glutathione were increased by H 2 O 2 and decreased by NAC. Moreover, the antibody recognizing the glutathionylated proteins co-precipitated and -localized with the cytoplasmic inactive form of p65NF-κB in H 2 O 2 -and NAC-treated cells, even when, in 1 mM NAC-treated cells, a part of p65 was glutathione-free and localized into the nucleus. Apoptotic cells were characterised principally by a cytoskeletal staining of glutathionylation and retention of NF-κB in the cytoplasmic region; whereas in proliferating cells, glutathionylated proteins were concentrated into the perinuclear region and p65NF-κB was traslocated into the nucleus. While cytoplasmic NF-κB retention correlated well with an increased apoptotic rate, a greater expression of this protein was observed in association with the NAC-dependent. In conclusion, our findings suggest that glutathionylation inhibits NF-κB activity causing reduced hepatocyte survival, which is common in several liver diseases.

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l-γ-Glutamyl-l-cysteinyl-glycine (glutathione; GSH) and GSH-related enzymes in the regulation of pro- and anti-inflammatory cytokines: a signaling transcriptional scenario for redox(y) immunologic sensor(s)?

Cited by 141 publications

References 332 publications

Longdan Xiegan Tang has immunomodulatory effects on CD4+CD25+ T cells and attenuates pathological signs in MRL/lpr mice

Longdan Xiegan Tang has immunomodulatory effects on CD4+CD25+ T cells and attenuates pathological signs in MRL/lpr mice

Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy

Glutathionylation of p65NF-κB correlates with proliferating/apoptotic hepatoma cells exposed to pro- and anti-oxidants

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