Document 0140 DOCN M94A0140 TI Transactivation of the human interleukin-6 gene by human T-lymphotropic virus type 1 Tax protein. DT 9412 AU Yamashita I; Katamine S; Moriuchi R; Nakamura Y; Miyamoto T; Eguchi K; Nagataki S; First Department of Internal Medicine, Nagasaki University School; of Medicine, Japan. SO Blood. 1994 Sep 1;84(5):1573-8. Unique Identifier : AIDSLINE MED/94348082 AB Interleukin-6 (IL-6) is a multifunctional cytokine that regulates both humoral and cellular immune responses. Accumulating evidence suggests that the infection of T cells and other cell types with human T-lymphotropic virus type 1 (HTLV-1) results in the constitutive expression of IL-6. However, the underlying molecular mechanisms are little understood. When a reporter plasmid, pIL6-CAT-E3, in which the human IL-6 enhancer/promoter region from -630 to +14 was linked to the bacterial chloramphenicol acetyltransferase (CAT) gene, was transfected, HTLV-1-infected but not -uninfected T-cell lines activated the IL-6 promoter. This indicated the presence of a factor transactivating the IL-6 gene in the infected cells. To evaluate the involvement of the HTLV-1-encoded transacting factor (Tax) in this transactivation, we examined the effect of transient cotransfection with the Tax-expression plasmid, pMAX-Neo, on the transcription from the IL-6 promoter by use of COS1 cells. The cotransfected COS1 has about six-times greater the CAT activity than that transfected with pIL6-CAT-E3 alone. The analysis of a series of deletions of the IL-6 promoter suggested that the region (-105/-47) containing a NF kappa B site was crucial for the Tax responsiveness. We further examined the effect of Tax on endogenous IL-6 gene expression using the Jurkat clone, JPX-9, stably transfected with pMAX-Neo. JPX-9 accumulated steady state transcripts of the endogenous IL-6 gene in response to the induction of Tax expression. Our findings indicate an important role of the Tax protein in the expression of IL-6 in cells infected with HTLV-1. DE Animal Base Sequence Cell Line Cercopithecus aethiops Chloramphenicol Acetyltransferase/BIOSYNTHESIS/GENETICS DNA Primers Enhancer Elements (Genetics) *Gene Expression Gene Products, tax/BIOSYNTHESIS/*METABOLISM Human HTLV-I/GENETICS/*PHYSIOLOGY Interleukin-6/*BIOSYNTHESIS/*GENETICS Kidney Molecular Sequence Data Polymerase Chain Reaction Promoter Regions (Genetics) Restriction Mapping RNA, Messenger/ANALYSIS/BIOSYNTHESIS Support, Non-U.S. Gov't *Trans-Activation (Genetics) Transfection Tumor Cells, Cultured JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).