title: Effects of florfenicol on LPS-induced nitric oxide and prostaglandin E₂ production in RAW 264.7 macrophages.
abstract: Florfenicol, an antibiotic commonly used to treat infections, has previously been shown to modulate lipopolysaccharide (LPS)-induced early cytokine responses by blocking the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the effects of florfenicol on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production as well as on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated murine RAW 264.7 macrophages. We also analysed the effects of florfenicol on mitogen-activated protein kinase (MAPK) pathways. Florfenicol significantly inhibited LPS-induced NO and PGE₂ production. Consistent with these observations, mRNA and protein expression of iNOS and COX-2 were also inhibited by florfenicol in a dose-dependent manner. Furthermore, phosphorylation of p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) in LPS-stimulated RAW 264.7 cells was suppressed by florfenicol. However, c-Jun N-terminal kinase (JNK) phosphorylation remained unaffected. Using specific inhibitors of ERK and p38, we found that florfenicol may inhibit NO and PGE₂ mostly through ERK and p38 pathway. These results suggest that florfenicol inhibits NO and PGE₂ production in conjunction with an inhibition of iNOS and COX-2 expression, at least partially via suppression of ERK1/2 and p38 MAPK phosphorylation.
authors.affiliation: Department of Animal Medicine, Agricultural College of Yanbian University, Longjing, Jilin 133400, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Huanzhang
authors.initials: H
authors.lastname: Xiong
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D013839:Thiamphenicol / Q000031:analogs & derivatives* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011725:Pyridines; D009569:Nitric Oxide; C035534:florfenicol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013839:Thiamphenicol; D015232:Dinoprostone; C093642:SB 203580