Journal
NEPHROLOGY
Volume 11, Issue 6, Pages 524-530Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1440-1797.2006.00695.x
Keywords
mesangial cell; NF-kappa B; roxithromycin; TGF-beta; thrombin; type IV collagen
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Background. Transforming growth factor-beta (TGF-beta) plays an important role in progression of renal injury. However, few materials which inhibit TGF-beta have been known. Roxithromycin (ROX), macrolide antibiotics, is known to have anti-inflammatory, immunomodulatory and tissue reparative effects besides its bacteriostatic activity, although the exact mechanism of its anti-inflammatory and immunomodulatory effects was not defined. We examined the effect of ROX on production of TGF-beta and type IV collagen by cultured human mesangial cells (HMC). Methods: Human mesangial cells were incubated with several concentrations of ROX and TGF-beta and type IV collagen levels in the culture supernatants were measured by enzyme-linked immunoassay. Amount of TGF-beta mRNA was also quantified by using a colourimetric mRNA quantification kit and semiquantitative reverse transcriptase polymerase chain reaction. We also examined the effect of ROX on tyrosine kinase, MAP kinase and NF-kappa B stimulated by thrombin. Results: Roxithromycin (0.1-10.0 mu g/mL) inhibited TGF-beta production by HMC in a dose- and time-dependent manner without inducing cell injury. ROX (10.0 mu g/mL) also inhibited mRNA expression of TGF-beta in HMC. Thrombin (5 U/mL) stimulated TGF-beta production by HMC and ROX significantly inhibited the stimulating effect of thrombin on TGF-beta production. ROX also inhibited the increment of type IV collagen production stimulated by thrombin. ROX (110.0 mu g/mL) suppressed the thrombin-induced NF-kappa B activation, although ROX did not inhibit the activation of tyrosine kinase and MAP kinase by thrombin. Conclusion: Roxithromycin has an inhibitory effect on TGF-beta production by HMC possibly via inhibition of NF-kappa B. ROX may be a potential agent for the treatment of glomerulosclerosis.
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