• Xuemei Zhang, Huanzhang Xiong, Hongyu Li, Lu Yu, and Xuming Deng.
• Department of Animal Medicine, Agricultural College of Yanbian University, Longjing, Jilin 133400, China.
• Fundam Clin Pharmacol. 2011 Oct 1; 25 (5): 591-8.

AbstractFlorfenicol, 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.© 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

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