Glutamine attenuates inflammation and NF-κB activation via Cullin-1 deneddylation

Singleton, Kristen D.; Wischmeyer, Paul E.

doi:10.1016/j.bbrc.2008.06.057

Cited by 44 publications

(39 citation statements)

References 21 publications

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“…Such a critical role for NF-B in mediating the anti-inflammatory effects of glutamine has also been reported for TNBS colitis in rats (23). Another report indicated that glutamine treatment leads to Cullin-1 deneddylation and in turn NF-B inhibition in mice (40). In contrast to the well-established role of NF-B in other forms of colitis (39), its role in GvHD is not completely clear.…”

Section: Discussionmentioning

confidence: 90%

Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model

Noth

Häsler

Stüber

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Although a profound barrier dysfunction has been reported, little is known about the pathophysiological mechanism evoking gastrointestinal graft-vs.-host disease (GI-GvHD) and apparent therapeutic options. The aim of this study was to evaluate the influence of oral glutamine on the course of GI-GvHD in an acute semiallogenic graft-vs.-host disease (GvHD) in irradiated B6D2F1 mice. An acute semiallogenic GvHD was induced by intraperitoneal injection of lymphocytes from C57BL/6 mice to irradiated B6D2F1 mice. Half of the GvHD animals received oral glutamine supplementation for 6 days started at the time of lymphocyte transfer. Six days after induction of the semiallogenic GvHD, jejunum specimens were prepared. The expression of the proinflammatory cytokine TNF-α and the tight junction protein occludin was investigated by PCR. Histological changes along with the apoptotic response were evaluated and intestinal permeability was assessed. Animals with GvHD showed a strong increase in paracellular permeability as a sign of the disturbed barrier function. TNF-α expression was significantly increased and the expression of the tight junction protein occludin decreased. GvHD led to mucosal atrophy, crypt hyperplasia, crypt apoptosis, and a disintegration of the tight junctions. Glutamine-treated mice showed reduced expression of TNF-α, increased occludin expression, fewer histological changes in the jejunum, smaller number of apoptotic cells in the crypt, and reduced gastrointestinal permeability. In conclusion, oral glutamine seems to have beneficial effects on the severity of inflammatory changes in the course of GvHD and might be a therapeutic option.

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Section: Discussionmentioning

confidence: 90%

Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model

Noth

Häsler

Stüber

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Glutamine and leucine are two important amino acids that dictate metabolism and signaling in proliferating cells and both have been demonstrated to have anti-inflammatory properties (Singleton and Wischmeyer, 2008; Sengupta et al, 2010). The requirement for these amino acids in starvation-induced PI3K phosphorylation was next tested by stimulating WT mEFs with HBSS or HBSS supplemented with L-glutamine, L-leucine, a mixture of non-essential amino acids (NEAA), or serum.…”

Section: Resultsmentioning

confidence: 99%

p85α SH2 Domain Phosphorylation by IKK Promotes Feedback Inhibition of PI3K and Akt in Response to Cellular Starvation

et al. 2012

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SUMMARY The IκB kinase (IKK) pathway is an essential mediator of inflammatory, oncogenic, and cell stress pathways. Recently IKK was shown to be essential for autophagy induction in mammalian cells independent of its ability regulate NF-κB, but the mechanism by which this occurs is unclear. Here we demonstrate that the p85 regulatory subunit of PI3K is an IKK substrate, phosphorylated at S690 in vitro and in vivo in response to cellular starvation. Cells expressing p85 S690A or inhibited for IKK activity exhibit increased Akt activity following cell starvation, demonstrating that p85 phosphorylation is required for starvation-induced PI3K feedback inhibition. S690 is in a conserved region of the p85 cSH2 domain, and IKK-mediated phosphorylation of this site results in decreased affinity for tyrosine-phosphorylated proteins and decreased PI3K membrane localization. Finally, leucine deprivation is shown to be necessary and sufficient for starvation-induced, IKK-mediated p85 phosphorylation and PI3K feedback inhibition.

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“…In our study the addition of 2 mM glutamine to incubation media appeared to promote the release of pro-inflammatory mediators [43], which could be reflective of experimental conditions, levels of extracellular HSP70 release or glutamine levels within the in vitro model. The cellular response to infection is a complex process co-ordinated by a wide range of intra-and extracellular mediators.…”

Section: LV Marino Et Al / Clinical Nutrition Xxx (2014) 1e7mentioning

confidence: 65%

The effect of 2 mMol glutamine supplementation on HSP70 and TNF-α release by LPS stimulated blood from healthy children

et al. 2015

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s u m m a r yObjective: Glutamine has been shown to promote heat shock protein 70 (HSP70) release both within experimental in vitro models of sepsis (2e10 mM) and in adults post trauma (0.5 g/kg), although the efficacy varies and is dependent on the model used. The effect of glutamine supplementation on HSP70 release in children is less clear. Therefore, the aim of this study was to investigate the effect of 2 mM glutamine added to incubation media on HSP70 and inflammatory mediator release in an in vitro model of paediatric sepsis using whole blood from healthy paediatric volunteers.Methods: An in vitro whole blood endotoxin stimulation model using 1 mg/ml lipopolysaccharide (LPS) over a 24 h time period was used to investigate the effects of 2 mM glutamine on HSP70 and inflammatory mediator release in healthy children. Results: The addition of 2 mM glutamine to the incubation media significantly increased HSP70 release over time (p < 0.05). This was associated with an early pro-inflammatory effect on TNF-a release at 4 h (p < 0.005) which was not seen at 24 h. There was a non significant trend towards higher levels of IL-6 and IL-10 following the addition of 2 mM glutamine, which appears to differ from the response reported in adult and animal models.Conclusion: Glutamine supplementation of incubation media promotes HSP70 and early TNF-a release in an in vitro model using blood samples from healthy children.

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Glutamine attenuates inflammation and NF-κB activation via Cullin-1 deneddylation

Cited by 44 publications

References 21 publications

Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model

Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model

p85α SH2 Domain Phosphorylation by IKK Promotes Feedback Inhibition of PI3K and Akt in Response to Cellular Starvation

The effect of 2 mMol glutamine supplementation on HSP70 and TNF-α release by LPS stimulated blood from healthy children

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