A regulatory role for astrocytes in HIV-1 encephalitis. An overexpression of eicosanoids, platelet-activating factor, and tumor necrosis factor-alpha by activated HIV-1-infected monocytes is attenuated by primary human astrocytes.

摘要: HIV-1-infected brain macrophages participate in neurologic dysfunction through their continual secretion of neurotoxins. We previously demonstrated that astroglial cells activate monocytes to produce such neurotoxic activities. In this study, the mechanism underlying these monocyte secretory activities was unraveled and found dependent on HIV-1's ability prime for activation. LPS stimulation resulted an overexpression eicosanoids, platelet-activating factor (PAF), TNF-alpha. This level HIV-1 infection stimulation. Cell cell interactions between activated virus-infected primary human astrocytes reduced secretions. The capacity deactivate was, notably, TGF-beta independent. Although constitutively produced latent 2, neither affected 2 production nor converted it into a bioactive molecule. Furthermore, addition rTGF-beta 1 or its Abs LPS-stimulated monocyte-astrocyte mixtures had no effect monokine production. contrast, rIL-10 dose-dependent decrease IL-10 mRNAs were detected monocytes, but not astrocytes, following treatment. These results suggest macrophage activation, major component brain, precipitates neuronal injury by causing synthesize neurotoxins are then regulated astrocytes. Astrocytes therefore, can play either positive negative roles disease depending prior findings begin unravel cellular control mechanisms influence cognitive motor dysfunctions individuals.