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In this study, we explored the anti\u2010inflammatory effect of FJU\u2010C28, a new 2\u2010pyridone\u2010based synthetic compound, on lipopolysaccharide (LPS)\u2010induced inflammation in vitro and in vivo models. FJU\u2010C28 suppressed the LPS\u2010induced mRNA and protein expression of iNOS, COX2 and proinflammatory cytokines. The cytokine protein array results showed that LPS stimulation enhanced the secretion of IL\u201010, IL\u20106, GCSF, Eotaxin, TNF\u03b1, IL\u201017, IL\u20101\u03b2, Leptin, sTNF RII, and RANTES. Conversely, the LPS\u2010induced secretion of RANTES, TIMP1, IL\u20106, and IL\u201010 was dramatically suppressed by FJU\u2010C28. FJU\u2010C28 suppressed the LPS\u2010induced expression of RANTES, but its parental compound FJU\u2010C4 was unable to diminish RANTES in cell culture media or cell lysates. FJU\u2010C28 blocked the secretion of IL\u20106 and RANTES in LPS\u2010activated macrophages by regulating the activation of JNK, p38 mitogen\u2010activated protein kinase (MAPK) and nuclear factor\u2010\u03baB (NF\u2010\u03baB). FJU\u2010C28 prevented the LPS\u2010induced decreases in lung function including vital capacity (VC), lung compliance (C chord), forced expiratory volume at 100\u00a0ms (FEV100), and forced vital capacity (FVC) in mice with LPS\u2010induced systemic inflammatory responses. FJU\u2010C28 also reduced neutrophil infiltration in the interstitium, lung damage and circulating levels of IL\u20106 and RANTES in mice with systemic inflammation. In conclusion, these findings suggest that FJU\u2010C28 possesses anti\u2010inflammatory activities to prevent endotoxin\u2010induced lung function decrease and lung damages by down\u2010regulating proinflammatory cytokines including IL\u20106 and RANTES via suppressing the JNK, p38 MAPK and NF\u2010\u03baB signaling pathways.<\/jats:p>","DOI":"10.1002\/prp2.876","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T12:35:19Z","timestamp":1634819719000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["FJU\u2010C28 inhibits the endotoxin\u2010induced pro\u2010inflammatory cytokines expression via suppressing JNK, p38 MAPK and NF\u2010\u03baB signaling pathways"],"prefix":"10.1002","volume":"9","author":[{"given":"Fang","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Respiratory Therapy Fu\u2010Jen Catholic University New Taipei City 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