title: Effect of insulin-like growth factor I on HIV type 1 long terminal repeat-driven chloramphenicol acetyltransferase expression.
abstract: In this study, we have investigated the ability of insulin-like growth factor I (IGF-I) to inhibit HIV long terminal repeat (LTR)-driven gene expression. Using COS 7 cells cotransfected with tat and an HIV LTR linked to a chloramphenicol acetyltransferase (CAT) reporter, we observed that physiological levels of IGF-I (10(-9) M) significantly inhibited CAT expression in a concentration- and time-dependent manner. IGF-I did not inhibit CAT expression in COS 7 cells transfected with pSVCAT, and did not affect CAT expression in the absence of cotransfection with tat. Transfection of HIV-1 proviral DNA into COS 7 cells +/- IGF-I resulted in a significant decrease (p < 0.05) in infectious virion production. Both IGF-I and Ro24-7429 inhibited LTR-driven CAT expression, while TNF-alpha-enhanced CAT expression was not affected by IGF-I. On the other hand, a plasmid encoding parathyroid hormone-related peptide exhibited dramatic additivity of inhibition of CAT expression in COS 7 cells. Finally, we show that in Jurkat or U937 cells cotransfected 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 can 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 various cell types employed.
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: R J
authors.initials: RJ
authors.lastname: Germinario
authors.forename: S P
authors.initials: SP
authors.lastname: Colby-Germinario
authors.forename: A
authors.initials: A
authors.lastname: Acel
authors.forename: R
authors.initials: R
authors.lastname: Chandok
authors.forename: K
authors.initials: K
authors.lastname: Davison
authors.forename: J
authors.initials: J
authors.lastname: Mak
authors.forename: L
authors.initials: L
authors.lastname: Kleiman
authors.forename: E
authors.initials: E
authors.lastname: Faust
authors.forename: M A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D019556:COS Cells; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D019169:Jurkat Cells; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology; D011758:Pyrroles; D020298:U937 Cells; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D015696:Gene Products, tat; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D011758:Pyrroles; D054322:tat Gene Products, Human Immunodeficiency Virus; D001569:Benzodiazepines; C070024:Ro 24-7429; D015847:Interleukin-4; D007334:Insulin-Like Growth Factor I; D015500:Chloramphenicol O-Acetyltransferase; D054303:HIV Reverse Transcriptase