Effect of roxithromycin on IL-8 synthesis and proliferation of nasal polyp fibroblasts.
Although several studies have demonstrated that low-dose, long-term 14-member macrolides (erythromycin (EM), roxithromycin (RXM), clarithromycin (CAM)) are effective in the treatment of chronic airway diseases like chronic sinusitis and diffuse panbronchiolitis (DPB), the mechanism of action of these drugs is not yet clear. Both these airway diseases are associated with an increase in the proliferation of fibroblasts. Moreover, fibroblasts are also an important source of proinflammatory cytokines such as interleukin-8 (IL-8), that play an important role in the pathogenesis of nasal polyps. Therefore, using primary fibroblast lines derived from nasal polyps, we investigated the effect of RXM on the synthesis of IL-8 and proliferation of nasal polyp fibroblasts (NPF). These fibroblasts were either treated with lipopolysaccharide (LPS) and RXM for 24 h, or pre-incubated with RXM for 24 h and then treated with LPS and RXM for 24 h. The level of IL-8 mRNA in NPF was analysed by reverse transcriptase-polymerase chain (RT-PCR) and the level of IL-8 in culture supernatants was measured by ELISA. Next, the proliferative capacity of NPF after treatment with RXM was analysed by cell counting and 3H-thymidine uptake. RXM had no effect on LPS-induced IL-8 synthesis by NPF. On the other hand, RXM suppressed the proliferation of NPF in a dose-dependent manner. These findings suggest that, although RXM cannot directly inhibit the synthesis of IL-8, it probably reduces IL-8 production by inhibiting the proliferation of NPF.
Nonaka
M
M
Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.
Pawankar
R
R
Saji
F
F
Yagi
T
T
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D009298:Nasal Polyps / Q000276:immunology* / Q000378:metabolism; D015575:Roxithromycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D008070:Lipopolysaccharides; D015575:Roxithromycin