Abstract
Human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein 120 has been shown to activate microglia, causing release of inflammatory and toxic factors. The P2X7 receptor, primarily expressed on microglia, is closely associated with inflammation. Naringin, a plant bioflavonoid, has anti-inflammatory and anti-oxidative properties. We hypothesized that P2X7 receptor mediated gp120-induced injury in primary cultured microglia, and that naringin would have a protective effect. We showed that HIV-1 gp120 peptide (V3 loop, fragment 308–331) appeared to induce apoptosis of primary cultured microglia. However, there was a decrease of microglia apoptosis in gp120+naringin group compared with gp120 group. Using qPCR, Western blot, and immunofluorescence, we showed that gp120 stimulated expression of P2X7 mRNA and receptor protein, and this stimulation was inhibited by naringin. Treatment with gp120 increased concentrations of eATP, TNFα and IL-1β, and these effects were inhibited by naringin. Taken together, these results suggested that gp120 contributed to microglial cell injury and neurotoxic activity by up-regulating expression of P2X7, in a naringin-protective manner.
Highlights
As the efficacy of antiretroviral therapy (ART) increases, the short-term mortality of acquired immune deficiency syndrome (AIDS) has decreased somewhat
Activated microglia amplify ATP stimulatory signals in an autocrine manner, leading to over-activation of microglia [13]. These findings suggest that P2X7 receptor may represent a new target for the prevention of microglia injury and the treatment of AIDS dementia complex (ADC) and other neuronal disorders associated with the inflammatory cascade
We explore the role of the P2X7 receptor in the pathogenesis of microglia injury, and we investigate the potential protective effect of naringin on gp120-induced primary cultured microglia injury
Summary
As the efficacy of antiretroviral therapy (ART) increases, the short-term mortality of acquired immune deficiency syndrome (AIDS) has decreased somewhat. AIDS is becoming a chronic disease with increased longevity [1]. The extended longevity of those living with HIV has led to a large number of diseases associated with inflammation, including cardiovascular disease, type II diabetes, cancer, and dementia [2]. The AIDS dementia complex (ADC), associated with both inflammatory and neurodegenerative processes, is a common complication of patients infected with HIV [3]. It is widely accepted that the infection and activation of microglia is closely related to neurologic dysfunction in HIV-associated dementia [4].
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