Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Eur J Pharmacol. 2011 Oct 1;668(1-2):264-70. doi: 10.1016/j.ejphar.2011.06.046. Epub 2011 Jul 8.
The anti-inflammatory properties of macrolides have been applied to the treatment of inflammatory airway diseases. Although the anti-inflammatory properties of fluoroquinolones have been reported, no reports are available regarding a newly developed fluoroquinolone, garenoxacin (GRNX). To examine the immunomodulatory effect of GRNX, we examined the transcription and secretion of inflammatory cytokines by human airway epithelial cells and monocytes stimulated with lipopolysaccharide (LPS). A human lung epithelial cell line (A549) and a human monocyte cell line (THP-1) were stimulated with LPS and exposed to different concentrations of GRNX. The transcription and secretion of interleukin 8 (IL-8) in both A549 and THP-1 cells was measured by real-time PCR and an enzyme-linked immunosorbent assay, respectively. Treatment with GRNX significantly inhibited the transcription and secretion of IL-8 induced by LPS-stimulated cells through inhibitory ERK1/2 phosphorylation. GRNX has anti-inflammatory activity through its capacity to alter the secretion of IL-8 from A549 and THP-1 cell lines. Our findings suggest that GRNX is suitable for the treatment of LPS-induced respiratory infection and inflammatory airway diseases.
大环内酯类的抗炎特性已被应用于治疗炎症性气道疾病。虽然已经报道了氟喹诺酮类的抗炎特性,但对于新开发的氟喹诺酮类药物加雷沙星(GRNX),尚无相关报道。为了研究 GRNX 的免疫调节作用,我们检测了人呼吸道上皮细胞和单核细胞在脂多糖(LPS)刺激下转录和分泌炎症细胞因子的情况。用 LPS 刺激人肺上皮细胞系(A549)和人单核细胞系(THP-1),并暴露于不同浓度的 GRNX。通过实时 PCR 和酶联免疫吸附试验分别测量 A549 和 THP-1 细胞中白细胞介素 8(IL-8)的转录和分泌。GRNX 通过抑制 ERK1/2 磷酸化显著抑制 LPS 刺激细胞诱导的 IL-8 的转录和分泌。GRNX 通过改变 A549 和 THP-1 细胞系中 IL-8 的分泌而具有抗炎活性。我们的研究结果表明,GRNX 适合治疗 LPS 诱导的呼吸道感染和炎症性气道疾病。