Department of Infectious Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Department of Infectious Diseases, The First Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
Mol Med Rep. 2018 Dec;18(6):5399-5408. doi: 10.3892/mmr.2018.9569. Epub 2018 Oct 22.
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)‑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 dose‑dependently decreased the viability of macrophages, and 8 and 16 µg/ml MXF prevented the LPS‑induced increase in TLR4, SPHK1, NF‑κB p65, TNF‑α and IL‑6 expression. The inhibition was most effective at a concentration of 16 µg/ml MXF, whereas, 64 µg/ml MXF exerted a pro‑inflammatory 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 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.
脓毒症是一种全身性炎症反应，是对危及生命的感染的反应，而巨噬细胞是炎症细胞因子的主要来源。莫西沙星（MXF）对革兰氏阳性和革兰氏阴性菌均具有抗菌活性。本研究探讨了 MXF 对脂多糖（LPS）刺激的巨噬细胞炎症反应和基因表达的影响。雄性 C57BL/6J 小鼠的腹腔巨噬细胞被分离出来，并与 LPS 和/或 MXF 一起处理。通过定量聚合酶链反应、western blot 和免疫荧光分析测定 Toll 样受体 4（TLR4）、鞘氨醇激酶 1（SPHK1）和核因子（NF）-κB 的 mRNA 和蛋白表达。用 ELISA 测定肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的表达。数据表明，MXF 呈剂量依赖性降低巨噬细胞活力，8 和 16 μg/ml MXF 可防止 LPS 诱导的 TLR4、SPHK1、NF-κB p65、TNF-α和 IL-6 表达增加。在 16 μg/ml MXF 的浓度下抑制作用最有效，而 64 μg/ml MXF 则发挥促炎作用。总的来说，数据表明 MXF 具有双向作用：较低浓度的 MXF（8 和 16 μg/ml）抑制炎症反应；然而，较高浓度的 MXF（64 μg/ml）对 LPS 处理的小鼠腹腔巨噬细胞具有促炎作用。总之，这些结果表明 MXF 在最佳剂量下作为炎症反应抑制剂的重要性。MXF 抑制炎症反应可能是通过 TLR4 信号传导介导的。
