{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:35:39Z","timestamp":1789536939128,"version":"build-2803163510"},"reference-count":50,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T00:00:00Z","timestamp":1474416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Innate Immun"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>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\u2009+\u20090.5% Asn; (4) LPS\u2009+\u20091.0% 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-\u03b1 concentration, and decreased the mRNA expression of intestinal TLR4, TLR4 downstream signals (myeloid differentiation factor 88, IL-1 receptor-associated kinase 1 and TNF-\u03b1 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).<\/jats:p>","DOI":"10.1177\/1753425916664124","type":"journal-article","created":{"date-parts":[[2016,8,23]],"date-time":"2016-08-23T20:18:03Z","timestamp":1471983483000},"page":"577-587","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":47,"title":["Asparagine improves intestinal integrity, inhibits TLR4 and NOD signaling, and differently regulates p38 and ERK1\/2 signaling in weanling piglets after LPS challenge"],"prefix":"10.1177","volume":"22","author":[{"given":"Shaokui","family":"Chen","sequence":"first","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulan","family":"Liu","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuying","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingan","family":"Pi","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-An Andy","family":"Hu","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People\u2019s Republic of China"},{"name":"Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Lin","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Odle","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,9,21]]},"reference":[{"key":"bibr1-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2006"},{"key":"bibr2-1753425916664124","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2013-6382"},{"key":"bibr3-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104192"},{"key":"bibr4-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1017\/S000711451400422X"},{"key":"bibr5-1753425916664124","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4808"},{"key":"bibr6-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0411183"},{"key":"bibr7-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12980"},{"key":"bibr8-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2009.06.005"},{"key":"bibr9-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022"},{"key":"bibr10-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1038\/srep12018"},{"key":"bibr11-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1051\/vetres:2007051"},{"key":"bibr12-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2013.01.027"},{"key":"bibr13-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.09.029"},{"key":"bibr14-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.04.019"},{"key":"bibr15-1753425916664124","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15069594"},{"key":"bibr16-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800056-JLR200"},{"key":"bibr17-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-164152"},{"key":"bibr18-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-008-0152-4"},{"key":"bibr19-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(93)90331-Z"},{"key":"bibr20-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-013-1565-2"},{"key":"bibr21-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)83660-3"},{"key":"bibr22-1753425916664124","doi-asserted-by":"crossref","first-page":"G164","DOI":"10.1152\/ajpcell.1996.271.1.C164","volume":"271","author":"Wang JY","year":"1996","journal-title":"Am J Physiol"},{"key":"bibr23-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114508911612"},{"key":"bibr24-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2013.12.006"},{"key":"bibr25-1753425916664124","unstructured":"NRC. Nutrient requirements of swine. 10th ed. Washington, DC: National Academic Press, 1998."},{"key":"bibr26-1753425916664124","first-page":"2450","volume":"24","author":"Li S","year":"2012","journal-title":"Chinese J Anim Nutr"},{"key":"bibr27-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-1191-9"},{"key":"bibr28-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1996.0245"},{"key":"bibr29-1753425916664124","doi-asserted-by":"publisher","DOI":"10.2527\/2002.802494x"},{"key":"bibr30-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"bibr31-1753425916664124","unstructured":"Luna LG. Manual of histologic staining methods of the armed forces institute of pathology. 3rd ed. New York: McGraw-Hill, 1968, p. 258."},{"key":"bibr32-1753425916664124","doi-asserted-by":"publisher","DOI":"10.5713\/ajas.2009.90100"},{"key":"bibr33-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"bibr34-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-7-research0034"},{"key":"bibr35-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-009-0269-0"},{"key":"bibr36-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/j.livsci.2007.07.003"},{"key":"bibr37-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1042\/cs0820471"},{"key":"bibr38-1753425916664124","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.3916"},{"key":"bibr39-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2015.07.001"},{"key":"bibr40-1753425916664124","doi-asserted-by":"publisher","DOI":"10.3945\/jn.114.202515"},{"key":"bibr41-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00407.2004"},{"key":"bibr42-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-14-19"},{"key":"bibr43-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090849"},{"key":"bibr44-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.09.006"},{"key":"bibr45-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-2980.2011.00525.x"},{"key":"bibr46-1753425916664124","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i5.656"},{"key":"bibr47-1753425916664124","first-page":"959","volume":"7","author":"Tang C","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"bibr48-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5240.1326"},{"key":"bibr49-1753425916664124","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.3.853.415a12_853_863"},{"key":"bibr50-1753425916664124","unstructured":"Chen SL. Animal physiology. 3rd ed. Beijing: Peking University Press, 2005."}],"container-title":["Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425916664124","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1753425916664124","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425916664124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:02:24Z","timestamp":1777460544000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1753425916664124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,21]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.1177\/1753425916664124"],"URL":"https:\/\/doi.org\/10.1177\/1753425916664124","relation":{},"ISSN":["1753-4259","1753-4267"],"issn-type":[{"value":"1753-4259","type":"print"},{"value":"1753-4267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,21]]}}}