Induction of cyclooxygenase-2 expression during HIV-1-infected monocyte-derived macrophage and human brain microvascular endothelial cell interactions.
Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD) is a neurodegenerative disease characterized by HIV infection and replication in brain tissue. HIV-1-infected monocytes overexpress inflammatory molecules that facilitate their entry into the brain. Prostanoids are lipid mediators of inflammation that result from cyclooxygenase-2 (COX-2) activity. Because COX-2 is normally induced during inflammatory processes, the aim of this study was to investigate whether COX-2 expression is up-regulated during monocyte-brain endothelium interactions. In vitro cocultures of HIV-infected macrophages and brain endothelium showed an up-regulation of COX-2 expression by both cell types. This up-regulation occurs via an interleukin-1beta (IL1beta)-dependent mechanism in macrophages and via an IL-1beta-independent mechanism in endothelial cells. Thus, interactions between HIV-infected monocytes and brain endothelium result in COX-2 expression and, as such, might contribute to the neuropathogenesis of HIV infection.
Pereira
C F
CF
Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation, University Medical Center, Utrecht, The Netherlands. C.F.Pereira@lab.azu.nl
Boven
L A
LA
Middel
J
J
Verhoef
J
J
Nottet
H S
HS
D015526:AIDS Dementia Complex / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D001921:Brain / Q000098:blood supply* / Q000821:virology; D002450:Cell Communication / Q000502:physiology*; D018920:Coculture Techniques; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D015497:HIV-1; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000201:enzymology* / Q000821:virology; D008565:Membrane Proteins; D009000:Monocytes / Q000166:cytology / Q000201:enzymology / Q000821:virology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases