Effect of insulin-like growth factor I on HIV type 1 long terminal repeat-driven chloramphenicol acetyltransferase expression

In this study, we have investigated the ability of insulin-like growth fact or I (IGF-I) to inhibit HPV long terminal repeat (LTR)-driven gene expressi on. Using COS 7 cells cotransfected with tat and an HIV LTR linked to a chl oramphenicol acetyltransferase (CAT) reporter, we observed that physiologic al levels of IGF-I (10(-9) M) significantly inhibited CAT expression in a c oncentration- and time-dependent manner. IGF-I did not inhibit CAT expressi on in COS 7 cells transfected with pSVCAT, and did not affect CAT expressio n in the absence of cotransfection with fat. Transfection of HIV-1 proviral DNA into COS 7 cells +/- IGF-I resulted in a significant decrease (p < 0.0 5) in infectious virion production. Both IGF-I and Ro24-7429 inhibited LTR- driven CAT expression, while TNF-alpha-enhanced CAT expression was not affe cted by IGF-I, On the other hand, a plasmid encoding parathyroid hormone-re lated peptide exhibited dramatic additivity of inhibition of CAT expression in COS 7 cells. Finally, we show that in Jurkat or U937 cells cotransfecte d with HIVLTRCAT/tat, IGF-I significantly inhibited CAT expression. Further , interleukin 4 showed in U937 cells inhibition of CAT expression that was not additive to IGF-I induced inhibition. Our data demonstrate that IGF-I c an specifically inhibit HIVLTRCAT expression, This inhibition may occur at the level of the tat/TAR interaction. Finally, this IGF-I effect is seen in target cell lines and similar paths of inhibition may be involved in the v arious cell types employed.