Differential regulation of TSG-14 expression in murine fibroblasts and peritoneal macrophages.
Tumor necrosis factor (TNF)-stimulated gene 14 (TSG-14, also termed PTX3) encodes a secreted glycoprotein whose carboxy-terminal half shares sequence similarity with the pentraxin family of acute phase proteins (C-reactive protein and serum amyloid P component). We compared TSG-14 mRNA expression in cultures of murine BALB/c 3T3 fibroblasts and thioglycollate-elicited peritoneal macrophages. TNF and interleukin-1 (IL-1) potently induced TSG-14 expression in 3T3 fibroblasts but not in peritoneal macrophages. Lipopolysaccharide (LPS) elicited TSG-14 expression in both cell types, but induction in 3T3 cells and macrophages showed several distinct characteristics. Whereas in 3T3 fibroblasts TSG-14 mRNA was rapidly up-regulated by LPS, expression in macrophages was substantially delayed. Furthermore, cycloheximide greatly reduced LPS-induced TSG-14 mRNA up-regulation in macrophages but not in 3T3 cells. Finally, interferon-gamma (IFN-gamma; but not IFN-alpha/beta) inhibited LPS-induced TSG-14 expression in macrophages and not in 3T3 fibroblasts. The antioxidant pyrrolidine dithiocarbamate inhibited LPS-induced nuclear factor-kappaB (NF-kappaB) activation and TSG-14 expression in macrophages. In contrast, IFN-gamma did not inhibit NF-kappaB function as measured by IkappaB-alpha and IkappaB-beta degradation, IkappaB-alpha resynthesis, or electrophoretic mobility shift analysis. Inhibition of LPS-induced TSG-14 mRNA expression by IFN-gamma in macrophages was also observed in the presence of cycloheximide and in cells from STAT1 null mice, suggesting that IFN-gamma inhibits TSG-14 expression through an unconventional mechanism.
Goodman
A R
AR
Department of Microbiology, New York University School of Medicine, NY 10016, USA.
Levy
D E
DE
Reis
L F
LF
Vilcek
J
J
D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D014176:Protein Biosynthesis; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D000683:Serum Amyloid P-Component / Q000235:genetics*; D013859:Thiocarbamates / Q000494:pharmacology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099153:Pentraxins
D002097:C-Reactive Protein; D003513:Cycloheximide; D004247:DNA; D004268:DNA-Binding Proteins; D007371:Interferon-gamma; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D000683:Serum Amyloid P-Component; D013859:Thiocarbamates; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins; C494080:Stat1 protein, mouse; C020972:pyrrolidine dithiocarbamic acid