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-1 beta (IL-1 beta)-dependent mechanism in macrophages and via an IL-1 beta-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

Oxidative stress and neuroAIDS:triggers, modulators and novel antioxidants

Neurological disorders represent one of the most common disturbances accompanying HIV infection. In the past few years, highly antiretroviral active therapy has significantly reduced the incidence of HIV-related diseases. However, neurological dysfunction in AIDS patients still remains an unresolved problem. Oxidative stress, which occurs in brain tissues of patients undergoing HIV infection and is implicated in cell death of both astroglia and neurones, has recently been suggested to play a role in the pathogenesis of neuroAIDS. Thus, a better understanding of the processes that trigger and modulate free radical formation in brain tissues of AIDS patients might help in a successful therapeutic approach to the neuropathogenesis of HIV infection