Lead ions abrogate lipopolysaccharide-induced nitric monoxide toxicity by reducing the expression of STAT1 and iNOS

Hua

et al. 2019

J. Agric. Food Chem.

Lactoferricin (Lfcin) B, derived from lactoferrin in whey, has attracted considerable attention because of its multiple biological functions. Zoonotic enterohemorrhagic Escherichia coli (EHEC) O157:H7 has adverse effects on intestinal epithelial barrier function, leading to serious intestinal disease. In this study, the EHEC O157:H7-induced intestinal dysfunction model was developed to investigate the effects of Lfcin B on EHEC O157:H7-induced epithelial barrier disruption and microbiota dysbiosis. Results showed that the inflammatory infiltration indexes in the jejunum of Lfcin B-treated animals were significantly decreased. Lfcin B administration also significantly improved ZO-1 and occludin expression following O157:H7induced injury. Finally, microbiota analysis of the cecal samples revealed that Lfcin B inhibited the O157:H7-induced abnormal increase in Bacteroides. Therefore, Lfcin B efficiently attenuated O157:H7-induced epithelial barrier damage and dysregulation of inflammation status, while maintaining microbiota homeostasis in the intestine, indicating that it may be an excellent food source for prevention and therapy of EHEC O157:H7-related intestinal dysfunction.

Section: Resultsmentioning

confidence: 99%

Oral Administration of Bovine Lactoferrin-Derived Lactoferricin (Lfcin) B Could Attenuate Enterohemorrhagic Escherichia coli O157:H7 Induced Intestinal Disease through Improving Intestinal Barrier Function and Microbiota

Hua

et al. 2019

J. Agric. Food Chem.

“…In this study, arginine administration inhibited the C. perfringens challenge-induced gene expressions involved in the JAK-STAT pathway. Dörpinghaus et al [53] reported that the inhibition of STAT1 expression downregulated iNOS transcription, which can alleviate LPS-induced cytotoxicity in macrophages and microglial cells. Ashino et al [54] have proven that the selective inhibition of JAK1/3 reduced STAT6 and STAT5 phosphorylation and Th2 cytokine production, which suppressed the development of airway hyperresponsiveness.…”

Section: Discussionmentioning

confidence: 99%

In vivo and in vitro protective effect of arginine against intestinal inflammatory response induced by Clostridium perfringens in broiler chickens

J Animal Sci Biotechnol

Gan

Shahid

et al. 2019

Background Necrotic enteritis is a widespread disease in poultry caused by Clostridium perfringens. We previously reported that dietary arginine supplementation protected the intestinal mucosa of broiler chickens with necrotic enteritis, but the related protective mechanisms remain unclear. The in vivo trial was designed as a 2 × 2 factorial arrangement to evaluated the effects of arginine supplementation on inflammatory responses, arginine transporters, arginine catabolism and JAK-STAT signalling pathway in broiler chickens challenged with C. perfringens or without C. perfringens . Furthermore, we validated the in vivo results using intestinal epithelial cells of chicken embryos. Results C. perfringens infection markedly increased gut gross pathological and histopathological lesion scores, promoted liver C. perfringens invasion, reduced serum arginine levels, and elevated jejunal mucosal lysozyme activities ( P < 0.05), but these effects were significantly reversed by arginine supplementation in vivo ( P < 0.05). The challenge significantly increased serum procalcitonin levels, jejunal mucosal iNOS activities and jejunal IL-6 , TGF-β3 , cationic amino acid transporter ( CAT ) -1 , and CAT-3 mRNA expression ( P < 0.05), whereas arginine supplementation significantly reduced jejunal IFN-γ , IL-1β , IL-6 , IL-10 , TGF-β3 , and CAT-3 mRNA expression ( P < 0.05). Arginine supplementation significantly attenuated the C. perfringens challenge-induced increases in jejunal iNOS , arginase 2, arginine decarboxylase, arginine:glycine amidinotransferase, JAK1 , JAK3 , STAT1 , and STAT6 mRNA expression ( P < 0.05). The in vitro experiment showed that C. perfringens challenge markedly increased cellular cytotoxicity and the mRNA expression of IL-1β , IL-8 , IL-10 , CAT-1 and CAT-3 ( P < 0.05), which were significantly reversed by 50 μmol/L and/or 400 μmol/L arginine pre-treatment ( P < 0.05). Conclusions Arginine prevented ...

“…Dörpinghaus et al (2016) investigated how Pb 2+ influences the cytotoxicity of LPS, focusing on its effect on the synthesis of NO and TNF-α by microglia BV-2 line and macrophages of the RAW264.7 line [ 110 ]. These lines are capable of producing both of these factors that contribute to the LPS-induced cytotoxicity.…”

Section: Influence Of Pb On Immune System Cellsmentioning

confidence: 99%

“…This results in a reduction in the amount of iNOS enzyme and ultimately leads to a reduced release of NO. Although studies on cell cultures suggest an increase in tolerance to LPS under the influence of Pb 2+ in vivo, blocking of NO production by Pb 2+ may cause impairment of pathogen removal, and thus prolong the fight against infections [ 110 ]. It is known that LPS induces apoptosis in macrophages [ 57 , 111 ].…”

Section: Influence Of Pb On Immune System Cellsmentioning

confidence: 99%

Lead (Pb) Exposure Enhances Expression of Factors Associated with Inflammation

Metryka

Chibowska

Gutowska

et al. 2018

IJMS

165

The human immune system is constantly exposed to xenobiotics and pathogens from the environment. Although the mechanisms underlying their influence have already been at least partially recognized, the effects of some factors, such as lead (Pb), still need to be clarified. The results of many studies indicate that Pb has a negative effect on the immune system, and in our review, we summarize the most recent evidence that Pb can promote inflammatory response. We also discuss possible molecular and biochemical mechanisms of its proinflammatory action, including the influence of Pb on cytokine metabolism (interleukins IL-2, IL-4, IL-8, IL-1b, IL-6), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α); the activity and expression of enzymes involved in the inflammatory process (cyclooxygenases); and the effect on selected acute phase proteins: C-reactive protein (CRP), haptoglobin, and ceruloplasmin. We also discuss the influence of Pb on the immune system cells (T and B lymphocytes, macrophages, Langerhans cells) and the secretion of IgA, IgE, IgG, histamine, and endothelin.