Ers and non-binders.AcknowledgmentsH.F. dedicates this work in memory of Jean-Gerard Guillet. We thank the ?study participants. We thank Laetitia Lacaze Buzy for providing Met-Enkephalin site clinicalToward a New Concept of HIV Vaccineand biological information on the patients and Ray Cooke for revising the manuscript.Author ContributionsConceived and designed the experiments: HF. Performed the experiments: JP PP SR GG DN. Eliglustat Analyzed the data: JP PP EL SR GG JLT DN HF. Wrote the paper: JP PP EL GG HF.
In modern pig farming, an increase in average litter size may enhance the potential for mortality from starvation and lack of innate immunity [1]. Hence, the development of immune system of neonatal piglets is particularly important. However, it is often underdeveloped [2]. For example, immunoglobulin quantitation, including IgA, IgG, and IgM, in the serum of young pigs decreased significantly at 14-d-old [3], and this may be due to an immature immune system, which is a main risk factor for infectious diseases in early life, especially the intestinal mucosal immunity [4]. It is well known that the intestine is the main entry route for foreign antigens, including invading pathogens that often lead to severe diarrhea [5]. Diarrhea in newborn piglets is a complicated problem caused by a variety of reasons, such as infectious agents like E. coli and rotavirus in small intestine [5,6]. Neonatal piglet diarrhea often leads to a significant decline in body weight gain. A well developed intestinal mucosal immune system can protect the mucous membranes against potentially dangerous microbes and some other toxic 23148522 elements 1662274 in the environment [4]. Thus, many attempts to explore strategies to improve intestinal mucosalimmunity and to understand the corresponding mechanisms have been made [7,8]. Arginine, a nutritionally essential amino acid in young mammals, has attracted much interest because of its powerful physiologic properties and pharmacological role in intestinal mucosa [9]. It has been reported that dietary arginine supplementation can enhance immune response in different rat models [7,10], improve intestinal function in weaned pigs [8], and stimulate mucosa growth in newborn piglets [11]. However, for milk-fed neonatal piglets, accumulated research indicates that arginine in sow’s milk cannot satisfy the requirement for piglets [12]. Meanwhile, the endogenous synthesis of arginine reduces dramatically in sucking piglets [13] owing to the decreasing activity of mitochondrial N-acetylglutamate synthase (NAGS) [9]. N-carbamylglutamate (NCG), a metabolically stable analogue of N-acetylglutamate (NAG), has been proved to increase the endogenous synthesis of arginine and plasma concentration of arginine by activating intestinal pyrroline-5-carboxylate synthase and carbamylphosphate synthase-1 [9]. Recent studies have proved that NCG supplementation could increase the serum arginine level, enhance pregnancy outcome in rats [14], and increase muscle protein synthesis in sow-reared piglets [15].Effect of N-Carbamylglutamate on PigletsHowever, few studies have investigated the effects of NCG on mucosa-associated lymphatic tissue (MALT) function and intestinal IgA. We hypothesized that dietary NCG supplementation, which activates endogenous synthesis of arginine and increases serum arginine levels, could improve intestinal mucosa immunity after an E. coli challenge. Therefore, the objective of this study was to evaluate whether NCG supplementation could attenuate gut inflammati.Ers and non-binders.AcknowledgmentsH.F. dedicates this work in memory of Jean-Gerard Guillet. We thank the ?study participants. We thank Laetitia Lacaze Buzy for providing clinicalToward a New Concept of HIV Vaccineand biological information on the patients and Ray Cooke for revising the manuscript.Author ContributionsConceived and designed the experiments: HF. Performed the experiments: JP PP SR GG DN. Analyzed the data: JP PP EL SR GG JLT DN HF. Wrote the paper: JP PP EL GG HF.
In modern pig farming, an increase in average litter size may enhance the potential for mortality from starvation and lack of innate immunity [1]. Hence, the development of immune system of neonatal piglets is particularly important. However, it is often underdeveloped [2]. For example, immunoglobulin quantitation, including IgA, IgG, and IgM, in the serum of young pigs decreased significantly at 14-d-old [3], and this may be due to an immature immune system, which is a main risk factor for infectious diseases in early life, especially the intestinal mucosal immunity [4]. It is well known that the intestine is the main entry route for foreign antigens, including invading pathogens that often lead to severe diarrhea [5]. Diarrhea in newborn piglets is a complicated problem caused by a variety of reasons, such as infectious agents like E. coli and rotavirus in small intestine [5,6]. Neonatal piglet diarrhea often leads to a significant decline in body weight gain. A well developed intestinal mucosal immune system can protect the mucous membranes against potentially dangerous microbes and some other toxic 23148522 elements 1662274 in the environment [4]. Thus, many attempts to explore strategies to improve intestinal mucosalimmunity and to understand the corresponding mechanisms have been made [7,8]. Arginine, a nutritionally essential amino acid in young mammals, has attracted much interest because of its powerful physiologic properties and pharmacological role in intestinal mucosa [9]. It has been reported that dietary arginine supplementation can enhance immune response in different rat models [7,10], improve intestinal function in weaned pigs [8], and stimulate mucosa growth in newborn piglets [11]. However, for milk-fed neonatal piglets, accumulated research indicates that arginine in sow’s milk cannot satisfy the requirement for piglets [12]. Meanwhile, the endogenous synthesis of arginine reduces dramatically in sucking piglets [13] owing to the decreasing activity of mitochondrial N-acetylglutamate synthase (NAGS) [9]. N-carbamylglutamate (NCG), a metabolically stable analogue of N-acetylglutamate (NAG), has been proved to increase the endogenous synthesis of arginine and plasma concentration of arginine by activating intestinal pyrroline-5-carboxylate synthase and carbamylphosphate synthase-1 [9]. Recent studies have proved that NCG supplementation could increase the serum arginine level, enhance pregnancy outcome in rats [14], and increase muscle protein synthesis in sow-reared piglets [15].Effect of N-Carbamylglutamate on PigletsHowever, few studies have investigated the effects of NCG on mucosa-associated lymphatic tissue (MALT) function and intestinal IgA. We hypothesized that dietary NCG supplementation, which activates endogenous synthesis of arginine and increases serum arginine levels, could improve intestinal mucosa immunity after an E. coli challenge. Therefore, the objective of this study was to evaluate whether NCG supplementation could attenuate gut inflammati.