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
Version of Record online: 29 JUL 2012
© 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology
Volume 17, Issue 6, pages 997–1005, August 2012
How to Cite
LI, H., ZHU, S., HE, S. and HAO, L. (2012), 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. Respirology, 17: 997–1005. doi: 10.1111/j.1440-1843.2012.02205.x
- Issue online: 29 JUL 2012
- Version of Record online: 29 JUL 2012
- Accepted manuscript online: 22 MAY 2012 11:25PM EST
- Received 11 August 2011; invited to revise 22 November 2011, 6 March 2012; revised 10 February 2012, 15 March 2012; accepted 15 March 2012 (Associate Editor: Darryl Knight)
- airway smooth muscle cell;
Background and 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.