Regulation of Complement Component C3 in Astrocytes by IL-1β and Morphine
Tóm tắt
Substances of abuse, such as opiates, and astroglial-derived proinflammatory cytokines, such as interleukin (IL)-1β, likely contribute to the neuroinflammatory and neurodegenerative processes observed in NeuroAIDS in injection drug users. Furthermore, uncontrolled synthesis and activation of complement component C3 in the brain can also lead to inflammation and neurodegeneration. We hypothesized that morphine may alter regulation of the C3 gene by IL-1β in astrocytes. Our studies demonstrate that IL-1β induces C3 promoter activity in a CAAT/enhancer-binding protein (C/EBP)-dependent manner. Inhibition of IL-1β mediated C3 promoter activation by the dominant negative mutant of p38-α mitogen-activated protein kinase suggests that IL-1β induces C3 expression through the activation of C/EBP. Morphine (0.01 μM) in combination with IL-1β further induced C3 promoter activity. Similarly, the C/EBP-β isoform liver activating protein and C/EBP-δ-induced C3 promoter activity were upregulated by morphine and IL-1β. Taken together, this study illustrates that morphine modulates IL-1β-mediated C3 expression in astrocytic cells.
Tài liệu tham khảo
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