title: Anti-inflammatory effects of moxifloxacin on rat airway smooth muscle cells exposed to allergen: Inhibition of extracellular-signal-regulated kinase and nuclear factor-κB activation and of interleukin-8 and eotaxin synthesis.
abstract: OBJECTIVE
  Moxifloxacin (MXF) has been shown to possess immunomodulatory properties in addition to its antimicrobial effects. We investigated the effects of MXF on cytokine secretion and signal transduction mechanisms in naive control and allergen-exposed airway smooth muscle cell (ASMC) stimulated with tumour necrosis factor (TNF)-α.
  
  
  METHODS
  An animal model was established. ASMC was derived from rat airway tissue and cultured in vitro, then incubated with 10 ng/mL of TNF-α. Interleukin (IL)-8 and eotaxin secretion were measured by enzyme-linked immunosorbent assay, and activation of extracellular-signal-regulated kinase (ERK)1/2 and nuclear factor (NF)-κB p65 was measured by western blotting, with or without the addition of MXF (20 µg/mL) and/or dexamethasone (DXM) (10(-6)  M).
  
  
  RESULTS
  Baseline IL-8 and eotaxin secretion did not differ between control and allergen-exposed cells. Stimulation with TNF-α increased IL-8 and eotaxin secretion, with increased IL-8 secretion by allergen-exposed compared with naive control ASMC, post-TNF-α stimulation (P = 0.001). Baseline phosphorylation of ERK1/2 (p-ERK1/2) and NF-κB p65 was higher in allergen-exposed than in control ASMC. TNF-α increased p-ERK1/2 and NF-κB p65 levels, with higher levels in allergen-exposed ASMC, post-TNF-α stimulation (P < 0.001). MXF and the combination of MXF with DXM suppressed the secretion of IL-8 and eotaxin, but DXM alone did not affect IL-8, post-TNF-α stimulation (P > 0.05). MXF, DXM and the combination of MXF with DXM inhibited TNF-α-stimulated p-ERK1/2 and NF-κB p65 levels by 34, 40 and 62%, and 33, 38 and 64%, respectively.
  
  
  CONCLUSIONS
  MXF suppressed the secretion of pro-inflammatory cytokines by allergen-exposed rat ASMC, partly by inhibiting NF-κB and ERK activation. DXM may have additional or synergistic effects with MXF.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, China. liht0419@163.com
authors.forename: Huiting
authors.initials: H
authors.lastname: Li
authors.forename: Shuyang
authors.initials: S
authors.lastname: Zhu
authors.forename: Shumin
authors.initials: S
authors.lastname: He
authors.forename: Lu
authors.initials: L
authors.lastname: Hao
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001372:Aza Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000096:biosynthesis* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D024841:Fluoroquinolones; D016209:Interleukin-8 / Q000096:biosynthesis*; D000077266:Moxifloxacin; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000485:Allergens; D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D001372:Aza Compounds; D054413:Chemokine CCL11; D024841:Fluoroquinolones; D016209:Interleukin-8; D016328:NF-kappa B; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D000077266:Moxifloxacin