HIV-TAT INCREASES IL-6 PRODUCTION BY AND PROLIFERATION OF AIDS-KS DERIVED CELLS (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

HIV-TAT INCREASES IL-6 PRODUCTION BY AND PROLIFERATION OF AIDS-KS DERIVED CELLS (MEETING ABSTRACT)

Proc Annu Meet Am Soc Clin Oncol; 10:A6 1991. Unique Identifier : AIDSLINE ICDB/91671338
Rezai A; Martinez-Maza O; Gaynor R; Kishimoto T; Hirano T; Mitsuyasu RT; Miles SA; UCLA AIDS Center, Los Angeles, CA 90024-1793

Abstract: AIDS-related Kaposi's sarcoma (AIDS-KS) is a multifocal proliferation of cells commonly observed in patients infected with human immunodeficiency virus (HIV). Previous studies suggested that the AIDS-KS spindle cells are of endothelial origin, produce multiple cytokines which have autocrine and paracrine growth properties, and proliferate in response to the transactivating protein of HIV, HIV-tat. We showed that AIDS-KS tissue produces large amounts of immunoreactive interleukin-6 (IL-6) and that AIDS-KS derived cell lines produce and respond to IL-6 in an autocrine growth loop. We investigated the effects of HIV-tat on IL-6 production by and proliferation of AIDS-KS derived cell lines. We found that IL-6 production by AIDS-KS cells can be increased by exposure to recombinant HIV-tat protein or by transfection of an HIV-tat expression vector. A control nonfunctional mutated HIV-tat expression vector had no effect. The increase in IL-6 production which was observed is accompanied by corresponding increases in cellular proliferation in the four cell lines examined. The increases in IL-6 production and proliferation of KS cells was inhibited by antisense but not sense IL-6 oligonucleotide polymers. No direct transactivation of the 5' flanking sequences of the IL-6 gene was found after cotransfection with HIV-tat in AIDS-KS derived cells. Our data suggests that HIV-tat increases IL-6 production by its KS cells, and this is associated with increased cell proliferation. The effects of HIV-tat on IL-6 production is presumably indirect as no direct effects on IL-6 gene regulatory elements were found.

Keywords: Acquired Immunodeficiency Syndrome/*PATHOLOGY Cell Division/*PHYSIOLOGY Cell Line Gene Products, tat/*PHYSIOLOGY Human Interleukin-6/*BIOSYNTHESIS Sarcoma, Kaposi's/*PATHOLOGY Tumor Cells, Cultured/*PATHOLOGY ABSTRACT

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