HIV-1 NONSPECIFICALLY STIMULATES PRODUCTION OF TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSFER IN PRIMARY ASTROCYTES

HIV-1 expression in monocytes/macrophages can be controlled by transfo rming growth factor-beta 1 (TGF-beta 1). TGF-beta 1 is present in astr ocytes surrounding HIV-l-infected monocyte/macrophages in brain tissue from patients with AIDS but not from seronegative, normal individuals . We sought to determine whether or not production of TGF-beta 1 can b e directly stimulated by HIV-1 in astrocytes. Astrocytes from neonatal rat cortex grown in primary culture were exposed to HIV-I virions for 24 h. One day later, TGF-beta 1 was measured in culture supernatants by a biological assay. HIV-1 caused 1.7-2.1-fold increase in extracell ular concentration of TGF-beta 1. TGF-beta 1 production also was stimu lated by recombinant HIV-I proteins gp120, p66 and p24. Gp120 labeled with fluorescein was visualized inside astrocytes and its stimulatory effect was not blocked by antibodies against rat CD4. The effect was n ot specific to HIV-1 and its proteins, because non-opsonized Latex par ticles and leucine methyl ester (LME) (known to be phagocytosed and en docytosed, respectively, by astrocytes) also stimulated TGF-beta 1 pro duction. The effect was inhibited by two inhibitors of the phago/endoc ytotic pathway, chloroquine and leupeptin. These results may be releva nt to the neuropathogenesis of HIV-1 infection.