Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells.
In this report, we show that in the human astroglioma cell line D54-MG, both interleukin-1 (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) enhance C3 gene expression in a time- and dose-dependent manner. Kinetic analysis demonstrates that after 96 h, C3 mRNA levels increase approximately 30-fold and 20-fold in response to IL-1 beta or TNF-alpha, respectively. C3 protein production increases proportionally, reaching levels 36-fold and 18-fold higher than untreated controls upon exposure to IL-1 beta or TNF-alpha, respectively. D54-MG cells require a minimal 1 h exposure to IL-1 beta in order to enhance C3 gene expression significantly, while 4 to 8 h are required for TNF-alpha. Simultaneous treatment of D54-MG cells with IL-1 beta and interferon-gamma (IFN-gamma) resulted in an additive increase in both C3 mRNA and protein expression, a finding not seen with the combination of TNF-alpha and IFN-gamma. Primary rat astrocytes also express increased C3 mRNA levels after 48 h in response to IL-1 beta (5.3-fold increase) and TNF-alpha (7-fold increase), while an additive effect was observed upon simultaneous treatment with both IL-1 beta and IFN-gamma. In the central nervous system (CNS), endogenous complement and cytokine production by astrocytes, and enhancement by IFN-gamma, a product of activated T cells often seen in the CNS in neural autoimmune disease, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis.
Barnum
S R
SR
Department of Microbiology, University of Alabama, Birmingham 35294.
Jones
J L
JL
Benveniste
E N
EN
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001254:Astrocytoma / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D003176:Complement C3 / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003176:Complement C3; D007375:Interleukin-1; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma