TRANSFORMING GROWTH-FACTOR-BETA-1 IN ADULT HUMAN MICROGLIA AND ITS STIMULATED PRODUCTION BY INTERLEUKIN-1

Ameboid microglia express human immunodeficiency virus 1 (HIV-1) more frequently than do ramified microglia, These two microglial subtypes m ight also differ in the frequency with which they express transforming growth factor-beta 1 (TGF-beta 1), a cytokine that regulates HIV-1 ex pression in monocytes. Results described here show that ameboid and ra mified microglia express TGF-beta 1. In brain tissues from HIV-1-infec ted individuals as compared with seronegative controls, ameboid rather than ramified microglia more frequently expressed TGF-beta 1, Ameboid microglia, isolated and cultured from postmortem adult human brain mo re frequently expressed TGF-beta 1 in presence of interleukin-1(IL-1), a cytokine that is elevated in brains of HIV-1-infected individuals w hen compared with seronegative controls. The stimulation of TGF-beta 1 by IL-1 was dose and time dependent, occurring with ameboid microglia isolated from either frontal cortex or globus pallidus but not midbra in pens, Ameboid microglia are similar to the RCA-1-positive cells tha t form clusters, called microglial nodules, in the brain of HIV-1-infe cted individuals. Pathologic conditions, such as disseminated microgli al nodules, are associated with HIV-1 encephalitis, direct infection o f the brain, and moderate to severe neurologic impairment. TGF-beta 1 expression in ameboid microglia may play a role in HIV-1 neuropathogen esis.