TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL REGULATION OF COMPLEMENT FACTOR-I (CFI) GENE-EXPRESSION IN HEP G2 CELLS BY INTERLEUKIN-6

We have investigated the effects of IL-1 and IL-6 on human complement factor I (CFI) production by Hep G2 cells. IL-6 treatment caused a dos e- and time-dependent increase in CFI secretion while IL-1 did not dem onstrate such effects. The increase in CFI synthesis correlated with i ncrease in CFI mRNA levels. The half-life of CFI mRNA in untreated cel ls was approx. 23 h and this was increased to 31 h (26% increase) foll owing induction with IL-6. The IL-6 induced increase in CFI gene expre ssion was inhibited by actinomycin D indicating regulatory effects at the level of transcription. Nuclear run-on experiments showed that IL- 6 increased the rate of CFI gene transcription 4.2-fold. Transient tra nsfection analysis of chloramphenicol acetyltransferase reporter gene constructs containing truncated segments of the 5'-flanking region of CFI gene showed that the cis-acting sequence(s) controlling the IL-6 i nducible transcription resides in an 83 bp region located between -738 bp and -655 bp relative to the transcription start site. Our results indicate that the upregulation of CFI gene expression by IL-6 involves a coordinate effort at the level of transcription and mRNA stability, with the enhanced rate of transcription being the principal mechanism . (C) 1998 Elsevier Science B.V. All rights reserved.