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Immunol."],"abstract":"<jats:p>Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>; however, whether eugenol alleviates  virus-mediated intestinal barrier damage and inflammation remains a mystery. Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Here, we found that eugenol could alleviate TGEV-induced intestinal functional impairment and inflammatory responses in piglets. Our results indicated that eugenol improved feed efficiency in TGEV-infected piglets. Eugenol not only increased serum immunoglobulin concentration (<jats:italic>IgG<\/jats:italic>) but also significantly decreased serum inflammatory cytokine concentration (<jats:italic>TNF-\u03b1<\/jats:italic>) in TGEV-infected piglets. In addition, eugenol also significantly decreased the expression of <jats:italic>NF-\u03baB<\/jats:italic> mRNA and the phosphorylation level of <jats:italic>NF-\u03baB P65<\/jats:italic> protein in the jejunum mucosa of TGEV-infected piglets. Eugenol increased villus height and the ratio of villus height to crypt depth in the jejunum and ileum, and decreased serum D-lactic acid levels. Importantly, eugenol increased tight junction protein (<jats:italic>ZO-1<\/jats:italic>) and mRNA expression levels of nutrient transporter-related genes (<jats:italic>GluT-2<\/jats:italic> and <jats:italic>CaT-1<\/jats:italic>) in the jejunum mucosa of TGEV-infected piglets. Meanwhile, compared with TGEV-infected IPEC-J2 cells, treatment with eugenol reduced the cell cytopathic effect, attenuated the inflammatory response. Interestingly, eugenol did not increase the expression of <jats:italic>ZO-1<\/jats:italic> and <jats:italic>Occludin<\/jats:italic> in IPEC-J2 cells. However, western blot and immunofluorescence results showed that eugenol restored TGEV-induced down-regulation of ZO-1 and Occludin, while BAY11-7082 (The NF-\u03baB specific inhibitor) enhanced the regulatory ability of eugenol. Our findings demonstrated that eugenol attenuated TGEV-induced intestinal injury by increasing the expression of <jats:italic>ZO-1<\/jats:italic> and <jats:italic>Occludin<\/jats:italic>, which may be related to the inhibition of <jats:italic>NF-\u03baB<\/jats:italic> signaling pathway. Eugenol may offer some therapeutic opportunities for coronavirus-related diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2022.921613","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T22:50:06Z","timestamp":1660690206000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-\u03baB signaling 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