UP-REGULATION OF INTERFERON-INDUCED INDOLEAMINE 2,3-DIOXYGENASE IN HUMAN MACROPHAGE CULTURES BY LIPOPOLYSACCHARIDE, MURAMYL TRIPEPTIDE, ANDINTERLEUKIN-1

Citation
Bd. Hissong et al., UP-REGULATION OF INTERFERON-INDUCED INDOLEAMINE 2,3-DIOXYGENASE IN HUMAN MACROPHAGE CULTURES BY LIPOPOLYSACCHARIDE, MURAMYL TRIPEPTIDE, ANDINTERLEUKIN-1, Cellular immunology, 160(2), 1995, pp. 264-269
Citations number
44
Categorie Soggetti
Cell Biology",Immunology
Journal title
ISSN journal
00088749
Volume
160
Issue
2
Year of publication
1995
Pages
264 - 269
Database
ISI
SICI code
0008-8749(1995)160:2<264:UOII2I>2.0.ZU;2-D
Abstract
The tryptophan decyclizing enzyme indoleamine 2,3-dioxygenase (IDO) wa s induced in human monocyte-derived macrophages (MDM) treated with hum an recombinant interferon-beta (IFN-beta) or interferon-gamma (IFN-gam ma). Treated cells exhibited dose-dependent increases in IDO when assa yed 48 hr after treatment. Cells exposed to IFN-gamma, were observed t o exhibit consistently higher peak levels of IDO when compared with ce lls incubated in the presence of IFN-beta. When IFN-beta-treated cells were incubated in the presence of specified amounts of bacterial lipo polysaccharide (LPS) or liposome-encapsulated muramyl tripeptide (MTP) , peak IDO activity increased such that enzyme activity was comparable to maximal activity observed with IFN-gamma-treated cells. LPS and MT P also upregulated IFN-gamma-mediated IDO activity when suboptimal amo unts of IFN-gamma were used. When macrophages were costimulated with v arious concentrations of human recombinant interleukin 1 alpha (IL-1 a lpha), along with either maximum-stimulating amounts of IFN-beta or su boptimal amounts of IFN-gamma, IDO activity was upregulated in a manne r similar to results obtained using the microbial products as stimuli. While neither IL-1 alpha or IL-1 beta was detected in culture superna tants from macrophages treated with either LPS or MTP (alone or in com bination with IFN), IL-1 alpha was detected in cell lysates of macroph ages treated with these upregulators. Although neutralizing antibody t o IL-1 alpha abolished the upregulatory effect of exogenous IL-1 alpha , it had no effect on upregulation by LPS or MTP. This suggests that a lthough LPS and MTP may induce production of cell-associated IL-1 alph a, upregulation of IDO activity by these agents is independent of IL-1 alpha production and may be mediated through distinct pathways. (C) 1 995 Academic Press, Inc.