Potentiation of interferon-induced indoleamine 2,3-dioxygenase mRNA in human mononuclear phagocytes by lipopolysaccharide and interleukin-1.
Previous studies have shown that interleukin-1 (IL-1) enhances interferon (IFN)-gamma-induced indoleamine 2,3-dioxygenase (IDO) enzymatic activity in human monocyte-derived macrophages by increasing expression of IDO mRNA. The objectives of this study were to see if IL-1 also enhances IFN-beta-induced IDO activity by increasing specific mRNA expression and to determine if lipopolysaccharide (LPS) enhances IFN-induced IDO activity in a similar manner. Macrophages were treated with combinations of IFN-beta or IFN-gamma as inducer and LPS or IL-1 as potentiator. After 48 h, IDO mRNA expression was assessed by RT-PCR, and IDO activity was determined by HPLC. LPS alone induced IDO mRNA expression and also increased IDO mRNA expression induced by either type of IFN. Furthermore, IL-1 enhanced IFN-beta-induced IDO mRNA expression. When IDO mRNA was assessed 6 h after treatment, mRNA was detected at concentrations of IFNs or potentiator or both in which enzymatic activity at 48 h was undetectable. Thus, although the mechanism of potentiation of IFN-induced IDO by LPS and by IL-1 involves increased expression of IDO mRNA, it appears that temporal differences in IDO mRNA expression are also important.
Hissong
B D
BD
Department of Microbiology, Miami University, Oxford, OH, USA.
Carlin
J M
JM
D002478:Cells, Cultured; D004357:Drug Synergism; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000235:genetics*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D007372:Interferons; D014366:Tryptophan Oxygenase