title: Asparagine improves intestinal integrity, inhibits TLR4 and NOD signaling, and differently regulates p38 and ERK1/2 signaling in weanling piglets after LPS challenge.
abstract: Asparagine (Asn), an activator of ornithine decarboxylase (ODC), stimulates cell proliferation in intestinal epithelial cells. We hypothesized that Asn can mitigate LPS-induced injury of intestinal structure and barrier function by regulating inflammatory signaling pathways. We executed the following experiment using weanling pigs for each of the groups: (1) non-challenged control; (2) LPS-challenged control; (3) LPS + 0.5% Asn; (4) LPS + 1.0% Asn. After 21-d feeding, pigs received an i.p. injection of either saline or LPS. Four h after injection, the mid-jejunum and mid-ileum samples were collected. We found that Asn restored ODC expression that was decreased by LPS treatment. Asn also restored intestinal morphology and barrier function that were impaired by LPS treatment. In addition, Asn down-regulated intestinal caspase-3 protein expression and TNF-α concentration, and decreased the mRNA expression of intestinal TLR4, TLR4 downstream signals (myeloid differentiation factor 88, IL-1 receptor-associated kinase 1 and TNF-α receptor-associated factor 6 and NOD1, NOD2 and their adaptor molecule (receptor-interacting serine/threonine-protein kinase 2). Moreover, Asn decreased p38 phosphorylation but increased ERK1/2 phosphorylation. Our results suggest that Asn improves intestinal integrity during an inflammatory insult, which appears to be related to the decrease of intestinal pro-inflammatory cytokine (via TLR4, NODs and p38) and of enterocyte apoptosis (via p38 and ERK1/2).
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Shaokui
authors.initials: S
authors.lastname: Chen
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shi
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Zhu
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Dingan
authors.initials: D
authors.lastname: Pi
authors.affiliation: 1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.|2 Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA.
authors.forename: Chien-An Andy
authors.initials: CA
authors.lastname: Hu
authors.affiliation: 3 Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: 3 Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Odle
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001216:Asparagine / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D020895:Enterocytes / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014886:Weaning; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D001216:Asparagine; D010105:Oxygenases; C114415:nitric oxide dioxygenase; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D009955:Ornithine Decarboxylase
keywords: Asparagine; inflammatory response; intestine; lipopolysaccharide; weanling piglets