IFN and virus-inducible expression of an immediate early gene, crg-2/IP-10, and a delayed gene, I-A alpha in astrocytes and microglia.
IFN-gamma is a potent macrophage activator and induces a number of early and delayed genes. crg-2, the presumed murine homologue of human IP-10, belongs to a family of proinflammatory chemokines and is induced as an immediate early gene in response to IFN-gamma in macrophages. In contrast, class II MHC or Ia genes which are essential for Ag presentation are induced as a delayed response to IFN-gamma. We studied the expression of crg-2 and compared it with Ia in astrocytes and microglia of the central nervous system since, like macrophages, these cells can also produce a number of cytokines, express Ia molecules, and present Ag. We showed that crg-2 mRNA was induced in astrocytes and microglia by IFN-gamma as well as a paramyxovirus, Newcastle disease virus (NDV). Crg-2 protein was detected in the cytoplasm and in the supernatants of IFN-gamma-treated astrocytes and microglia. IFN-gamma and NDV or UV irradiated-NDV (UV-NDV) also induced Ia mRNA in these cells. The kinetics of expression of crg-2 and Ia mRNA were compared in the same systems. While crg-2 mRNA appeared within 2 h and reached a maximum in 6 to 8 h, Ia mRNA was not detected before 8 h. Cycloheximide superinduced crg-2 mRNA induced by IFN-gamma or UV-NDV but it abolished Ia mRNA induction by the same stimuli. The induction of crg-2 in astrocytes and microglia likely contributes to the development of immune-mediated inflammation in response to viruses or in autoimmune diseases of the central nervous system.
Vanguri
P
P
Department of Neurology, University of Maryland, School of Medicine, Baltimore 21201.
Farber
J M
JM
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D017781:Genes, Immediate-Early; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology*; D017628:Microglia / Q000378:metabolism*; D015846:Monokines / Q000235:genetics* / Q000378:metabolism; D009522:Newcastle disease virus / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C489313:Crg2 protein, rat; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D015846:Monokines; D012333:RNA, Messenger; D007371:Interferon-gamma