RESUMO
Sepsis is a systemic inflammatory condition in response to lifethreatening infections, and macrophages are a key source of inflammatory cytokines. Moxifloxacin (MXF) has antibacterial activity in Grampositive and Gramnegative bacteria. The present study investigated the effects of MXF on a lipopolysaccharide (LPS)stimulated inflammatory response and gene expression in macrophages. Peritoneal macrophages were isolated from male C57BL/6J mice and treated with LPS and/or MXF. The mRNA and protein expression of tolllike receptor 4 (TLR4), sphingosine kinase 1 (SPHK1) and nuclear factor (NF)κB was determined by quantitative polymerase chain reaction, western blotting and immunofluorescence analysis. The expression of tumor necrosis factor (TNF)α and interleukin (IL)6 was determined with ELISAs. The data demonstrated that MXF dosedependently decreased the viability of macrophages, and 8 and 16 µg/ml MXF prevented the LPSinduced increase in TLR4, SPHK1, NFκB p65, TNFα and IL6 expression. The inhibition was most effective at a concentration of 16 µg/ml MXF, whereas, 64 µg/ml MXF exerted a proinflammatory effect. Collectively, the data demonstrated a bidirectional effect of MXF: Lower MXF concentrations (8 and 16 µg/ml) inhibited the inflammatory response; however, a higher MXF concentration (64 µg/ml) had a proinflammatory effect on LPStreated mouse peritoneal macrophages. In conclusion, these results suggested the importance of MXF as an inhibitor of the inflammatory response at an optimal dose. MXF inhibition of the inflammatory response may be mediated by TLR4 signaling.
