Bidirectional effects of moxifloxacin on the pro‑inflammatory response in lipopolysaccharide‑stimulated mouse peritoneal macrophages.

Sepsis is a systemic inflammatory condition in response to life-threatening infections, and macrophages are a key source of inflammatory cytokines. Moxifloxacin (MXF) has antibacterial activity in Gram-positive and Gram-negative 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 toll-like receptor 4 (TLR4), sphingosine kinase 1 (SPHK1) and nuclear factor (NF)-B was determined by quantitative polymerase chain reaction, western blotting and immunofluorescence analysis. The expression of tumor necrosis factor (TNF)- and interleukin (IL)-6 was determined with ELISAs. The data demonstrated that MXF dose-dependently decreased the viability of macrophages, and 8 and 16 mu g/ml MXF prevented the LPS-induced increase in TLR4, SPHK1, NF-B p65, TNF- and IL-6 expression. The inhibition was most effective at a concentration of 16 mu g/ml MXF, whereas, 64 mu g/ml MXF exerted a pro-inflammatory effect. Collectively, the data demonstrated a bidirectional effect of MXF: Lower MXF concentrations (8 and 16 mu g/ml) inhibited the inflammatory response; however, a higher MXF concentration (64 mu g/ml) had a pro-inflammatory effect on LPS-treated 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.