Alanyl-glutamine ameliorates lipopolysaccharide-induced inflammation and barrier function injury in bovine jejunum epithelial cells

Zhang, Xianglun; Tan, Xiaodong; Liu, Yifan; You, Wei; Liu, Guifen; Liu, Xiaomu; Jin, Qinian; Chen, Wei; Wan, Fachun; Zhao, Hongbo

doi:10.1139/bcb-2018-0320

Cited by 12 publications

(6 citation statements)

References 37 publications

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“…Interestingly, the upregulated mRNA levels of ileal IFN-γ, IL-1β , and TLR4 were abolished in E. coli- infected broilers by dietary HWG supplementation, suggesting that HWG might inhibit TLR4 signaling pathway to suppress the production of inflammatory cytokines, consequently alleviated the E. coli -induced inflammation ( Liu et al, 2017 ). Previous studies have demonstrated that functional amino acids, such as Gln and Gly, could relieve the LPS-induced intestinal injury ( Xu et al, 2018 ; Zhang et al, 2019 ). In the present study, high proportion of Gln, Gly and proline in the HWG may be responsible for the intestinal inflammatory alleviation of E. coli -infected broilers.…”

Section: Discussionmentioning

confidence: 99%

Dietary hydrolyzed wheat gluten supplementation ameliorated intestinal barrier dysfunctions of broilers challenged with Escherichia coli O78

Wen-yu²,

Kim

et al. 2022

Poultry Science

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This study aimed to investigate a protective effect of hydrolyzed wheat gluten ( HWG ) on Escherichia coli ( E. coli )-induced intestinal barrier dysfunctions in broilers. Broilers fed a basal diet unsupplemented or supplemented with HWG (0.5% or 1%) were intraperitoneally injected with either E. coli O78 suspension (10 8 CFU/mL) or equal volume of vehicle on d 18 of age. Blood and tissue samples were collected 3rd d post infection. The results showed that E. coli -infection increased immune-organ indexes of spleen and thymus, enhanced serum diamine oxidase ( DAO ) level, impaired ileal villus structure and reduced tight junction mRNA levels ( Occludin, Claudin-1, ZO-1, P < 0.05), while increased mRNA levels of inflammatory cytokines ( TNF-α, IFN-γ, IL-1β, IL-6, IL-8 ) and TLR4 in the ileum of broilers ( P < 0.05). The effects of E. coli O78 challenge on organ indexes of spleen and thymus, serum DAO level, mRNA levels of tight junctions were alleviated by 1% HWG supplementation, the upregulations of IL-1β and TLR4 were prevented by 0.5% HWG supplementation ( P < 0.05). In addition, increased IFN-γ of E. coli -infected broilers was abrogated by 0.5% or 1% HWG supplementation ( P < 0.05). In summary, dietary HWG supplementation ameliorated intestinal barrier dysfunctions triggered by E. coli -infection in the ileum of broilers. HWG supplementation might be a nutritional strategy to improve the intestinal mucosal barrier function of broilers.

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Section: Discussionmentioning

confidence: 99%

Dietary hydrolyzed wheat gluten supplementation ameliorated intestinal barrier dysfunctions of broilers challenged with Escherichia coli O78

Wen-yu²,

Kim

et al. 2022

Poultry Science

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“…In addition, Ala-Gln is usually used in enteral nutrition. Clinical and experimental investigations demonstrated that Ala-Gln increased the expression of tight junction proteins and maintained the intestinal mucosal thickness and villus height to preserve the gut barrier function (Liu et al, 1997;Zhang et al, 2019). Although Ala-Gln is widely used in various conditions, so far, it has no application reports in the field of ophthalmology.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects Oncorneal Endothelium During Intracameral Irrigation Using N-(2)-l-alanyl-l-Glutamine

Jin

Wang

et al. 2020

Front. Pharmacol.

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Corneal endothelial disease is a global sight-threatening disease, and corneal transplantation using donor corneas remains the sole therapeutic option. A previous work demonstrated that N (2)-alanyl-glutamine (Ala-Gln) protected against apoptosis and cellular stress, and maintained intestinal tissue integrity. In this pursuit, the present study aimed to examine the effect of Ala-Gln in the protection of the corneal endothelium and expand its range of potential clinical applications. Mice in the control group were intracamerally irrigated with Ringers lactate injection, whereas those in the experimental group were irrigated with Ringers lactate injection containing Ala-Gln. The mean intraocular pressure increased to 44 ± 3.5 mm Hg during intracameral irrigation (normal range 10.2 ± 0.4 mmHg). In vivo confocal microscopy results showed that the addition of Ala-Gln protected the morphology, structure, and density of the corneal endothelial cells. Optical Coherence Tomography (OCT) measurements showed that corneal thickness was not significantly different between the two groups, because of the immediate corneal edema after irrigation, but the addition of Ala-Gln obviously promoted the recovery of the corneal edema. Scanning electron microscopy indicated that the corneal endothelial cells were severely ruptured and exfoliated in the Ringer's group accompanied with cellular edema, when compared with the Ala-Gln group. The intracameral irrigation using Ala-Gln protected the structure and expression of cytoskeleton and Na-K-ATPase, which exhibited a regular distribution and significantly increased expression in comparison to Ringer's group. Furthermore, Ala-Gln maintained the mitochondrial morphology and increased the activity of mitochondria. Moreover, transmission electron microscopy showed that intracameral irrigation of Ala-Gln reversed the ultrastructural changes induced by the acute ocular hypertension in mice. Our study demonstrates that the intracameral irrigation of Ala-Gln effectively maintained the corneal endothelial pump function and barrier function by protecting the mitochondrial function and preventing the rearrangement of cytoskeleton in acute ocular hypertension in mice.

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“…Whether Ala-Gln has a direct anti-inflammatory effect on macrophages has not been fully investigated. A previous study has shown that Ala-Gln could enhance cell viability and inhibit the expression of inflammatory mediators in LPS-stimulated bovine intestinal epithelial cells [ 51 ]. Here, in LPS-treated RAW264.7 cells, we found that Ala-Gln significantly reduced the elevated expression of IL-6, TNF-α, and RANTES, indicating the direct anti-inflammatory effects of Ala-Gln in macrophages.…”

Section: Discussionmentioning

confidence: 99%

Alanyl-Glutamine Protects against Lipopolysaccharide-Induced Liver Injury in Mice via Alleviating Oxidative Stress, Inhibiting Inflammation, and Regulating Autophagy

Ying

Zheng

et al. 2022

Antioxidants

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Acute liver injury is a worldwide problem with a high rate of morbidity and mortality, and effective pharmacological therapies are still urgently needed. Alanyl-glutamine (Ala-Gln), a dipeptide formed from L-alanine and L-glutamine, is known as a protective compound that is involved in various tissue injuries, but there are limited reports regarding the effects of Ala-Gln in acute liver injury. This present study aimed to investigate the protective effects of Ala-Gln in lipopolysaccharide (LPS)-induced acute liver injury in mice, with a focus on inflammatory responses and oxidative stress. The acute liver injury induced using LPS (50 μg/kg) and D-galactosamine (D-Gal) (400 mg/kg) stimulation in mice was significantly attenuated after Ala-Gln treatment (500 and 1500 mg/kg), as evidenced by reduced plasma alanine transaminase (ALT) (p < 0.01, p < 0.001), aspartate transaminase (AST) (p < 0.05, p < 0.001), and lactate dehydrogenase (LDH) (p < 0.01, p < 0.001) levels, and accompanied by improved histopathological changes. In addition, LPS/D-Gal-induced hepatic apoptosis was also alleviated by Ala-Gln administration, as shown by a greatly decreased ratio of TUNEL-positive hepatocytes, from approximately 10% to 2%, and markedly reduced protein levels of cleaved caspase-3 (p < 0.05, p < 0.001) in liver. Moreover, we found that LPS/D-Gal-triggered oxidative stress was suppressed after Ala-Gln treatment, the effect of which might be dependent on the elevation of SOD and GPX activities, and on GSH levels in liver. Interestingly, we observed that Ala-Gln clearly inhibited LPS/D-Gal exposure-induced macrophage accumulation and the production of proinflammatory factors in the liver. Furthermore, Ala-Gln greatly regulated autophagy in the liver in LPS/D-Gal-treated mice. Using RAW264.7 cells, we confirmed the anti-inflammatory role of Ala-Gln-targeting macrophages.

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Alanyl-glutamine ameliorates lipopolysaccharide-induced inflammation and barrier function injury in bovine jejunum epithelial cells

Cited by 12 publications

References 37 publications

Dietary hydrolyzed wheat gluten supplementation ameliorated intestinal barrier dysfunctions of broilers challenged with Escherichia coli O78

Dietary hydrolyzed wheat gluten supplementation ameliorated intestinal barrier dysfunctions of broilers challenged with Escherichia coli O78

Protective Effects Oncorneal Endothelium During Intracameral Irrigation Using N-(2)-l-alanyl-l-Glutamine

Alanyl-Glutamine Protects against Lipopolysaccharide-Induced Liver Injury in Mice via Alleviating Oxidative Stress, Inhibiting Inflammation, and Regulating Autophagy

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