Production of interferon-gamma by microglia.
Neural cells do not usually interact with immune cells because of the lack of major histocompatibility complex (MHC) antigen expression. Interferon-gamma (IFN-gamma) enables this interaction via induction of MHC antigen expression in neural cells. Thus, IFN-gamma is a critical cytokine for the development of central nervous system (CNS) pathologies. IFN-gamma, however, is considered to be produced exclusively by lymphoid cells. Here, we show for the first time that murine microglia produce IFN-gamma in response to IL-12 and/or IL-18, using RT-PCR detection of IFN-gamma mRNA and Western blotting and immunohistochemical analysis for cytoplasmic expression of IFN-gamma. 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-gamma and MHC antigens.
Kawanokuchi
J
J
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusaku, Nagoya 464-8601, Japan.
Mizuno
T
T
Takeuchi
H
H
Kato
H
H
Wang
J
J
Mitsuma
N
N
Suzumura
A
A
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D000906:Antibodies; D000949:Histocompatibility Antigens Class II; D020382:Interleukin-18; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma