Antifibrosis effect of intrferonγ (IFNγ) and rapamycin (Rapa) in immortal human hepatic stellate cells *
To examine the antifibrosis effect of interferony (IFNγ) and Rapa an immortalized human hepatic stellate cell line, TWNT-4, was established by introducing human telomerase reverse transcriptase (hTERT) into LI 90 cells. The TWNT-4 cells were confirmed to express plateletderived growth factorβreceptor (PDGF-βR) and α-smooth muscle actin (α-SMA) by immunostaining. Interferony (IFNγ), which is known to inhibit human hepatic, stellate cell activation, could not inhibit collagen type 1 (α1) under a condition of 24 hour incubation at more than 1000 U/ml concentration. Incubation of IFNγ at a low concentration of 100 U/ml, for 14 days, however, inhibit collagen type 1 (α1) production in both RNA and protein levels. An immunosuprressive agent Rapa, also inhibited collagen type 1 (α1) production proportionally at a concentration of 1 to 10 ng/ml. When both IFNγ and Rapa were added to the incubation medium for 14 days at the one tenth of the usual concentration of each drug, collagen type 1 (α1) expression was equally inhibited. IFNγ and Rapa also inhibited production of TGF-β1 hepatic stellate cell PDGF-βR, and α-SMA. apoptosis of TWNT-4 cells occurred as a result of adenovirus-mediated TRAIL cDNA transfer. These results confirmed that IFNγ and Rapa inhibit collagen expression in hepatic stellate cells, resulting in an antifibrosis effect. Therefore these drugs could have a clinical application for the prevention of fibrosis in liver cirrhosis. (Accepted on August 28, 2002) Kawasaki Igakkaishi 28 (3) : 185-197, 2002
