REGULATION OF LECITHIN-CHOLESTEROL ACYLTRANSFERASE BY TGF-BETA AND INTERLEUKIN-6

The human hepatoma derived HepG2 cells were treated with transforming growth factor-beta (TGF-beta) or interleukin-6 (IL-6) +/- dexamethason e. The effects of treatment on lecithin:cholesterol acyltransferase (L CAT) catalytic activity and mRNA level as well as on the apolipoprotei n A-I (ape A-I) mRNA level were determined. Both the LCAT activity in medium from treated HepG2 cells and the LCAT mRNA level were decreased by TGF-beta. There was no significant effect of IL-6 +/- dexamethason e, neither on the LCAT activity nor on LCAT mRNA levels. Treatment wit h dexamethasone alone resulted in a decreased LCAT activity in spite o f a slight increase in LCAT mRNA level. The apo A-I mRNA level was red uced after treatment with TGF-beta and increased after treatment with IL-6 +/- dexamethasone and dexamethasone alone. To analyze if the effe cts on mRNA levels were caused by transcriptional or post-transcriptio nal mechanisms, run-on experiments on isolated nuclei from treated Hep G2 cells and mRNA degradation experiments were performed. The transcri ption rate of the LCAT gene was not affected by TGF-beta, but was incr eased (50-100%) after treatment with IL-6 +/- dexamethasone and dexame thasone alone. The transcription rate of the apo A-I gene was reduced (20%) by TGF-beta and increased (30-60%) by IL-6 +/- dexamethasone and dexamethasone alone. Both dexamethasone and TGF-beta increased the ra te of LCAT mRNA degradation. These results show that the reduced LCAT mRNA level after treatment with TGF-beta was caused by post-transcript ional mechanisms.