Glutamine decreases intestinal nuclear factor kappa B activity and pro-inflammatory cytokine expression after traumatic brain injury in rats

Chen, Gang; Shi, Jinjie; Qi, Meng; Yin, Hui; Hang, Chun-Hua

doi:10.1007/s00011-007-7101-7

Cited by 37 publications

(18 citation statements)

References 38 publications

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“…Similarly, other investigators have demonstrated that exogenous glutamine and progesterone, administered following TBI, decrease IL-1, TNF-a, and IL-6 levels in both intestinal and brain tissue (Chen, Shi, Jin, et al, 2008;Chen, Shi, Qi, et al, 2008). Since ghrelin has been shown to have antiinflammatory properties and ghrelin mediates intestinal homeostasis, it was our hypothesis that ghrelin would protect against GI dysfunction caused by TBI.…”

supporting

confidence: 52%

The Hormone Ghrelin Prevents Traumatic Brain Injury Induced Intestinal Dysfunction

Bansal

Ryu

Blow

et al. 2010

Journal of Neurotrauma

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Intestinal barrier breakdown following traumatic brain injury (TBI) is characterized by increased intestinal permeability, leading to bacterial translocation, and inflammation. The hormone ghrelin may prevent intestinal injury and have anti-inflammatory properties. We hypothesized that exogenous ghrelin prevents intestinal injury following TBI. A weight-drop model created severe TBI in three groups of anesthetized Balb/c mice. Group TBI: animals underwent TBI only; Group TBI/ghrelin: animals were given 10 mg of ghrelin intraperitoneally prior and 1 h following TBI; Group sham: no TBI or ghrelin injection. Intestinal permeability was measured 6 h following TBI by detecting serum levels of FITC-Dextran after injection into the intact ileum. The terminal ileum was harvested for histology, expression of the tight junction protein MLCK and inflammatory cytokine TNF-a. Permeability increased in the TBI group compared to the sham group (109.7 AE 21.8 mg/mL vs. 32.2 AE 10.1 mg/mL; p < 0.002). Ghrelin prevented TBI-induced permeability (28.3 AE 4.2 mg/mL vs. 109.7 AE 21.8 mg/mL; p < 0.001). The intestines of the TBI group showed blunting and necrosis of villi compared to the sham group, while ghrelin injection preserved intestinal architecture. Intestinal MLCK increased 73% compared to the sham group ( p < 0.03). Ghrelin prevented TBI-induced MLCK expression to sham levels. Intestinal TNF-a increased following TBI compared to the sham group (46.2 AE 7.1 pg/mL vs. 24.4 AE 2.2 pg/mL p < 0.001). Ghrelin reduced TNF-a to sham levels (29.2 AE 5.0 pg/mL; p ¼ NS). We therefore conclude that ghrelin prevents TBI-induced injury, as determined by intestinal permeability, histology, and intestinal levels of TNF-a. The mechanism for ghrelin mediating intestinal protection is likely multifactorial, and further studies are needed to delineate these possibilities.

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supporting

confidence: 52%

The Hormone Ghrelin Prevents Traumatic Brain Injury Induced Intestinal Dysfunction

Bansal

Ryu

Blow

et al. 2010

Journal of Neurotrauma

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“…mice with the hormone ghrelin following TBI blocks the increase in TNF-a and MLCK expression along with the increase in intestinal permeability. 21 Similarly, electrical stimulation of the vagus nerve before TBI in mice, 25,26 increasing glutamine levels in the diet following TBI in rats, 27,28 or injection of the antioxidantsedative propofol following TBI in rats 29 blocks the increase in TNF-a expression as well as the increase in intestinal permeability following TBI. Conversely, mice deficient for nuclear factor erythroid 2-related factor 2 (Nrf2) have higher TNF-a expression and higher intestinal permeability than wild-type mice following TBI.…”

Section: Tbi Activates a Feedback Loop That Enhances Intestinal Permementioning

confidence: 99%

The gut reaction to traumatic brain injury

Katzenberger

Ganetzky

Wassarman

2015

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“…In animal models of sepsis, glutamine (2 to 10 mM) [19,30] has been shown to attenuate the release of proinflammatory cytokines through the inhibition of IKK (IkKa) and the subsequent downregulatory effect on the NF-kB and MAPK pathways [28], attenuating the release of IL-6 and TNF-a [19,28,[31][32][33], IL-8 [34], IL-1 b [32], and IL-10 [31]. The release of inflammatory mediators appears to be dependent on the HSP70 release, because the effect of glutamine supplementation is lost in the absence of HSP70 gene upregulation, using HSP70.1/3 knockout mice, with a subsequent uncontrolled release of TNF-a and IL-6, increasing the rate of mortality compared with normal wild-type mice [35].…”

Section: Discussionmentioning

confidence: 99%

An in vitro model to consider the effect of 2 mM glutamine and KNK437 on endotoxin-stimulated release of heat shock protein 70 and inflammatory mediators

et al. 2016

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Please cite this article as: Marino LV, Pathan N, Meyer R, Wright VJ, Habibi P, An in vitro model to consider the effect of 2mM glutamine and KNK437 on endotoxin stimulated release of HSP70 and inflammatory mediators, Nutrition (2015), doi: 10.1016/j.nut.2015.09.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Objective: Glutamine has been shown to promote heat shock protein 70 (HSP70) release both within 2 experimental in vitro models of sepsis and in adults with septic shock. 3Methods: An in vitro whole blood endotoxin stimulation assay was used to investigate the effects of 4 2mM glutamine and an inhibitor of HSP70 (KNK437) on the release of HSP70 and inflammatory 5 mediators in healthy adult volunteers. 6Results: 2mM glutamine significantly increased HSP70 levels over time (p<0.05). HSP70 release had a 7 positive correlation at 4 hours with IL-1β (r=0.51, p=0.03), an inverse correlation with TNF-α (r=-8 0.56, p=0.02) and IL-8 levels (r=-0.52, p=0.03), and there were no significant correlations between 9 HSP70 and IL6 or IL-10 or glutamine. Glutamine supplementation significantly (p<0.05) attenuated 10 the release of IL-10 at 4 hours and IL-8 at 24 hours, compared to conditions without glutamine. In 11 endotoxin stimulated blood there were no significant differences in the release of IL-6, TNF-α and IL-12 1β with glutamine supplementation at 4 and 24 hours. However, glutamine supplementation (2mM) 13 appeared to attenuate the release of inflammatory mediators (IL-1β, IL-6, TNF-α), although this 14 effect was not statistically significant. The addition of KNK 437, an HSP70 inhibitor significantly 15 diminished HSP70 release which resulted in lower levels of inflammatory mediators (p<0.05). 16Conclusion: Glutamine supplementation promotes HSP70 release in an experimental model of 17 sepsis. Following the addition of KNK437 the effects of glutamine on HSP70 and inflammatory 18 mediator release appear to be lost, suggesting the HSP70 in part orchestrates the inflammatory 19 mediator response to sepsis. The clinical implications require further investigation.

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Glutamine decreases intestinal nuclear factor kappa B activity and pro-inflammatory cytokine expression after traumatic brain injury in rats

Abstract: The results of the present study suggest that the therapeutic benefit of post-TBI glutamine supplementation might be due to its inhibitory effects on intestinal NF-kappaB activation and pro-inflammatory cytokine expression.

Cited by 37 publications

References 38 publications

The Hormone Ghrelin Prevents Traumatic Brain Injury Induced Intestinal Dysfunction

The Hormone Ghrelin Prevents Traumatic Brain Injury Induced Intestinal Dysfunction

The gut reaction to traumatic brain injury

An in vitro model to consider the effect of 2 mM glutamine and KNK437 on endotoxin-stimulated release of heat shock protein 70 and inflammatory mediators

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