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Roxithromycin inhibits transforming growth factor‐β production by cultured human mesangial cells
Author(s) -
YAMABE HIDEAKI,
SHIMADA MICHIKO,
KAIZUKA MITSUAKI,
NAKAMURA MASAYUKI,
KUMASAKA RYUICHIRO,
MURAKAMI REIICHI,
FUJITA TAKESHI,
NAKAMURA NORIO,
OSAWA HIROSHI,
OKUMURA KEN
Publication year - 2006
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.2006.00695.x
Subject(s) - roxithromycin , thrombin , mesangial cell , microbiology and biotechnology , collagenase , tyrosine kinase , transforming growth factor , transforming growth factor beta , cytokine , suramin , tgf beta 1 , endocrinology , medicine , enzyme , chemistry , biology , biochemistry , kidney , platelet , receptor , antibiotics , erythromycin
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.