@article{10.1371/journal.pone.0082877, doi = {10.1371/journal.pone.0082877}, author = {Liu, Jung-Sen AND Jung, Fang AND Yang, Shih-Hsing AND Chou, Shang-Shing P. AND Huang, Jhih-Liang AND Lu, Chang-Lin AND Huang, Guan-Lin AND Yang, Pan-Chyr AND Lin, Jau-Chen AND Jow, Guey-Mei}, journal = {PLOS ONE}, publisher = {Public Library of Science}, title = {FJU-C4, a New 2-Pyridone Compound, Attenuates Lipopolysaccharide-Induced Systemic Inflammation via p38MAPK and NF-κB in Mice}, year = {2013}, month = {12}, volume = {8}, url = {https://doi.org/10.1371/journal.pone.0082877}, pages = {1-10}, abstract = {Despite advances in antibiotic therapy and intensive care, the mortality caused by systemic inflammatory response syndrome and severe sepsis remains high. The use of anti-inflammatory agents to attenuate inflammatory response during acute systemic inflammatory reactions may improve survival rates. Here we show that a newly synthesized 2-pyridone compound (FJU-C4) can suppress the expression of late inflammatory mediators such as iNOS and COX-2 in murine macrophages. The pro-inflammatory cytokines, including TNFα, IL-1β, and IL-6, were dose-dependently suppressed by FJU-C4 both in mRNA and protein levels. In addition, the expression of TNFα was inhibited from as early as 2 hours after exposure to LPS stimulation. The production of mature pro-inflammatory cytokines was also suppressed by pretreatment with FJU-C4 in either cell culture medium or mice serum when stimulated by LPS. FJU-C4 prolongs mouse survival and prevents mouse death from LPS-induced systemic inflammation when the dose of FJU-C4 is over 5 mg/kg. The activities of ERK, JNK, and p38MAPK were induced by LPS stimulation on murine macrophage cell line, but only p38MAPK signaling was dramatically suppressed by pretreatment with the FJU-C4 compound in a dose-dependent manner. NF-κB activation also was suppressed by FJU-C4 compound. These findings suggest that the FJU-C4 compound may act as a promising therapeutic agent against inflammatory diseases by inhibiting the p38MAPK and NF-κB signaling pathway.}, number = {12}, }