{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T06:15:08Z","timestamp":1777702508542,"version":"3.51.4"},"reference-count":42,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"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":["Journal of Interferon &amp; Cytokine Research"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:p>\n                    Arginine is one of the host semiessential amino acids with diverse biological activities, and arginine depletion is associated with the incidence of many diseases. Arginine depletion induced by diet-derived interferon gamma (IFN-\u03b3) leads to malignant transformation and impaired milk quality in healthy lactating bovine mammary epithelial cells (BMECs). However, the molecular mechanism of IFN-\u03b3-induced arginine depletion is unclear. In this study, the BMEC cell line, mammary alveolar cells-large T antigen cells (MAC-T), was stimulated with IFN-\u03b3 (10\u2009ng\/mL) for 24\u2009h, and cellular arginine and ornithine quantified by liquid chromatography-tandem mass spectrometry. Carnosine synthase 1 (\n                    <jats:italic toggle=\"yes\">CARNS1<\/jats:italic>\n                    ) was identified from RNA-seq data,\n                    <jats:italic toggle=\"yes\">CARNS1<\/jats:italic>\n                    knockdown was achieved using an shRNA interfering plasmid. The expression levels of\n                    <jats:italic toggle=\"yes\">CARNS1<\/jats:italic>\n                    , argininosuccinate synthetase 1 (\n                    <jats:italic toggle=\"yes\">ASS1<\/jats:italic>\n                    ), mitogen-activated protein kinase 11 (\n                    <jats:italic toggle=\"yes\">p38<\/jats:italic>\n                    MAPK), and phosphorylated\n                    <jats:italic toggle=\"yes\">(p)-p38<\/jats:italic>\n                    , and their cognate genes, were analyzed by Western blotting and real-time quantitative polymerase chain reaction. The results showed that IFN-\u03b3 inhibited the biosynthesis of arginine, but enhanced its catalysis via disruption of key enzymes involved in arginine metabolism. IFN-\u03b3 also inhibited the expression of\n                    <jats:italic toggle=\"yes\">CARNS1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">ASS1<\/jats:italic>\n                    , and cationic amino acid transporter 1, while activating the expression and phosphorylation of p38. However, knockdown of\n                    <jats:italic toggle=\"yes\">CARNS1<\/jats:italic>\n                    reduced arginine level and ASS1 expression and block of either the IFN-\u03b3 receptor IFN-\u03b3 receptor 2 or p38 relieved both the expression of Carnosine synthase 1 (CARNS1) and ASS1. In summary, these results indicate that IFN-\u03b3 induced arginine depletion through inhibition of CARNS1 signaling via activation of p38 in BMECs. These findings provide a novel insight for IFN-\u03b3-related disease control strategies in dairy cows.\n                  <\/jats:p>","DOI":"10.1089\/jir.2022.0025","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T10:17:52Z","timestamp":1659003472000},"page":"501-512","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Carnosine Synthase 1 Contributes to Interferon Gamma-Induced Arginine Depletion via Mitogen-activated Protein Kinase 11 Signaling in Bovine Mammary Epithelial Cells"],"prefix":"10.1177","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3613-8709","authenticated-orcid":false,"given":"Jing","family":"Miao","sequence":"first","affiliation":[{"name":"Department of Preventative Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-6284","authenticated-orcid":false,"given":"Fengyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Preventative Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meina","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition, College of Animal Science, Jilin University, Changchun, P.R. China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changhai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition, College of Animal Science, Jilin University, Changchun, P.R. 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China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5872-1842","authenticated-orcid":false,"given":"Liancheng","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Preventative Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, P.R. 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