[Effects of cyclosporin A combined with T4 on collagen IV production, coll alpha 1 (IV) mRNA and TGF beta 1 mRNA expression in cultured human mesangial cells].

OBJECTIVE: To investigate the effects of single cyclosporin A (CsA), tripcholorlide (T4) or both on renal fibrosis. METHODS: Collagen IV concentrations in the supernatants of human mesangial cells (HMCs) in culture were measured by ELISA. Collagen type IV alpha 1 mRNA (Coll alpha 1 IV mRNA) and transforming growth factor beta 1 (TGF beta 1) mRNA expression were tested by RT-PCR. RESULTS: CsA regulated HMC collagen IV production biphysically, i.e., 1.0 microgram/ml CsA increased collagen synthesis while 0.01-0.1 microgram/ml CsA decreased its formation. T4 enhanced collagen IV production in a dose dependent manner. Combination of the two drugs in lower doses could reach the same degree of immunosuppression as a higher dose of CsA did but with less fibrogenesis. Both CsA and T4 up-regulated HMC Coll alpha 1 (IV) mRNA and TGF beta 1 mRNA expression. The degree of Coll alpha 1 (IV) mRNA expression in different groups were in accordance with that of TGF beta 1 mRNA. CONCLUSIONS: Both CsA and T4 regulate extracellular matrix formation which may be mediated by TGF beta 1. Combination of the two drugs in lower dose results in less fibrosis than a higher dose of CsA.