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