Evidence for stimulation of the transforming growth factor beta 1 promoter by HIV-1 Tat in cells derived from CNS.
Infection by human immunodeficiency virus type 1 (HIV-1), the etiologic agent of the acquired immunodeficiency syndrome (AIDS), is often complicated with a high incidence of neurologic disorders. It is believed that HIV-1, in addition to infecting both macroglial and microglial cells, may influence the expression of several strategic genes of uninfected neighboring or latently infected brain cells. It is suspected that the viral-encoded transregulatory protein, Tat, facilitates cross-communications between these cells. In support of this concept, earlier studies demonstrated that Tat is released from the infected cells, and has the capacity to be taken up by the uninfected cells and exert its biological activity on the responsive gene. Recent studies in several laboratories suggest the involvement of Tat in altering the expression of a limited number of cellular regulatory factors which, in turn, may mediate the altered physiology of the cells. In this communication, we demonstrate the ability of the HIV-1 Tat protein to increase expression of transforming growth factor beta 1 (TGF-beta 1), a cytokine with potent immunosuppressive activity, in human astrocytic glial cells. Implications of the Tat-mediated induction of TGF-beta 1 expression and cytokine involvement in the regulation of immune response and central nervous system (CNS) pathology are discussed.
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Jefferson Institute of Molecular Medicine, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Taylor
J P
JP
Khalili
K
K
Amini
S
S
D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002874:Chromosome Mapping; D015870:Gene Expression / Q000187:drug effects; D015696:Gene Products, tat / Q000494:pharmacology*; D015497:HIV-1; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014407:Tumor Cells, Cultured; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D054322:tat Gene Products, Human Immunodeficiency Virus