title: Anti-inflammatory effects of garenoxacin on IL-8 production and ERK1/2 activation induced by lipopolysaccharides in A549 and THP-1 cells.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishimatsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.forename: Noriho
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kakugawa
authors.forename: Hanako
authors.initials: H
authors.lastname: Fujita
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D017291:Clarithromycin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D048628:Ketolides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D024841:Fluoroquinolones; D007155:Immunologic Factors; D016209:Interleukin-8; D048628:Ketolides; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000667:Ampicillin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D017291:Clarithromycin; C106791:telithromycin; C419689:garenoxacin