Production of interferon-γ by microglia

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Abstract
Neural cells do not usually interact with immune cells because of the lack of major histocompatibility complex (MHC) antigen expression. Interferon-γ (IFN-γ) enables this interaction via induction of MHC antigen expression in neural cells. Thus, IFN-γ is a critical cytokine for the development of central nervous system (CNS) pathologies. IFN-γ, however, is considered to be produced exclusively by lymphoid cells. Here, we show for the first time that murine microglia produce IFN-γ in response to IL-12 and/or IL-18, using RT-PCR detection of IFN-γ mRNA and Western blotting and immunohistochemical analysis for cytoplasmic expression of IFN-γ. Stimulation of microglia with IL-12 and IL-18 resulted in MHC class II mRNA expression in microglia. Since IL-12 and IL-18 are produced in the CNS by glial cells, these cytokines may play a critical role in the initiation of neural immune cell interaction and the induction of autoimmune processes in the CNS via induction of IFN-γ and MHC antigens.