Abstract
We have recently demonstrated that long-term exposure of cigarette smoke condensate (CSC) to HIV-uninfected (U937) and -infected (U1) macrophages induce packaging of pro-inflammatory molecules, particularly IL-1β, in extracellular vesicles (EVs). Therefore, we hypothesize that exposure of EVs derived from CSC-treated macrophages to CNS cells can increase their IL-1β levels contributing to neuroinflammation. To test this hypothesis, we treated the U937 and U1 differentiated macrophages once daily with CSC (10 µg/ml) for 7 days. Then, we isolated EVs from these macrophages and treated these EVs with human astrocytic (SVGA) and neuronal (SH-SY5Y) cells in the absence and presence of CSC. We then examined the protein expression of IL-1β and oxidative stress related proteins, cytochrome P450 2A6 (CYP2A6), superoxide dismutase-1 (SOD1), catalase (CAT). We observed that the U937 cells have lower expression of IL-1β compared to their respective EVs, confirming that most of the produced IL-1β are packaged into EVs. Further, EVs isolated from HIV-infected and uninfected cells, both in the absence and presence of CSC, were treated to SVGA and SH-SY5Y cells. These treatments showed a significant increase in the levels of IL-1β in both SVGA and SH-SY5Y cells. However, under the same conditions, the levels of CYP2A6, SOD1, and catalase were only markedly altered. These findings suggest that the macrophages communicate with astrocytes and neuronal cells via EVs-containing IL-1β in both HIV and non-HIV setting and could contribute to neuroinflammation.