Roxithromycin inhibits transforming growth factor-β production by cultured human mesangial cells

SUMMARY: Background:  Transforming growth factor-β (TGF-β) plays an important role in progression of renal injury. However, few materials which inhibit TGF-β 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-β and type IV collagen by cultured human mesangial cells (HMC). Methods:  Human mesangial cells were incubated with several concentrations of ROX and TGF-β and type IV collagen levels in the culture supernatants were measured by enzyme-linked immunoassay. Amount of TGF-β 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-κB stimulated by thrombin. Results:  Roxithromycin (0.1–10.0 µg/mL) inhibited TGF-β production by HMC in a dose- and time-dependent manner without inducing cell injury. ROX (10.0 µg/mL) also inhibited mRNA expression of TGF-β in HMC. Thrombin (5 U/mL) stimulated TGF-β production by HMC and ROX significantly inhibited the stimulating effect of thrombin on TGF-β production. ROX also inhibited the increment of type IV collagen production stimulated by thrombin. ROX (10.0 µg/mL) suppressed the thrombin-induced NF-κB activation, although ROX did not inhibit the activation of tyrosine kinase and MAP kinase by thrombin. Conclusion:  Roxithromycin has an inhibitory effect on TGF-β production by HMC possibly via inhibition of NF-κB. ROX may be a potential agent for the treatment of glomerulosclerosis.