Transforming growth factor-beta1 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 might also differ in the frequency with which they express transforming growth factor-beta1 (TGF-beta1), a cytokine that regulates HIV-1 expression in monocytes. Results described here show that ameboid and ramified microglia express TGF-beta1. In brain tissues from HIV-1-infected individuals as compared with seronegative controls, ameboid rather than ramified microglia more frequently expressed TGF-beta1. Ameboid microglia, isolated and cultured from postmortem adult human brain more frequently expressed TGF-beta1 in presence of interleukin-1(IL-1), a cytokine that is elevated in brains of HIV-1-infected individuals when compared with seronegative controls. The stimulation of TGF-beta1 by IL-1 was dose and time dependent, occurring with ameboid microglia isolated from either frontal cortex or globus pallidus but not midbrain pons. Ameboid microglia are similar to the RCA-1-positive cells that form clusters, called microglial nodules, in the brain of HIV-1-infected individuals. Pathologic conditions, such as disseminated microglial nodules, are associated with HIV-1 encephalitis, direct infection of the brain, and moderate to severe neurologic impairment. TGF-beta1 expression in ameboid microglia may play a role in HIV-1 neuropathogenesis.
da Cunha
A
A
Laboratory of Cell Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Jefferson
J J
JJ
Tyor
W R
WR
Glass
J D
JD
Jannotta
F S
FS
Cottrell
J R
JR
Resau
J H
JH
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D015497:HIV-1; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D012323:RNA Processing, Post-Transcriptional; D013268:Stimulation, Chemical; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D007375:Interleukin-1; D016212:Transforming Growth Factor beta