© 1997 American Heart Association, Inc.
Articles |
Cytokine Modulation of LDL Oxidation by Activated Human Monocytes
From the Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
Correspondence to Martha Cathcart, PhD, Department of Cell Biology, Building NC1, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail cathcam{at}cesmtp.ccf.org
Abstract There is considerable evidence to suggest that
cytokines modulate the pathological cellular events that occur
in human atherosclerosis. We sought to determine the
effects of T-helper-lymphocyte (TH)-1- and
TH2-type cytokines on the ability of human
monocytes to oxidize LDL, one of the pathological processes believed to
occur in atherosclerosis. The ability of opsonized
zymosan (ZOP)-activated human monocytes to oxidize LDL in a
24-hour period was significantly enhanced by pretreatment of the
monocytes with the TH2 cytokines, interleukin
(IL)-4, or IL-13 compared with untreated monocytes. In contrast,
interferon (IFN)-
, a TH1 cytokine, inhibited LDL
oxidation by activated monocytes. Treatment with IFN- also
prevented the IL-4- and IL-13-mediated enhancement of LDL oxidation by
ZOP-activated monocytes. Untreated or cytokine-treated
unactivated monocytes did not oxidize LDL. The enhancement of
LDL oxidation mediated by IL-4 or IL-13 treatment was not due to a
mitogenic effect of the cytokines on the monocytes,
nor to modulation of superoxide anion (O2-)
production. The cytokine regulation of
15-lipoxygenase (LO) in the monocytes was also
examined. IL-4 and IL-13 induction of 15-LO mRNA and 15-LO activity in
the monocytes was confirmed, as was the previously reported inhibition
of induction by IFN-. In summary, IL-4 and IL-13 enhance the ability
of activated human monocytes to oxidize LDL, whereas IFN-
inhibits the cell-mediated oxidation. The up- and downregulation of
activated monocyte-mediated LDL oxidation by these
cytokines correlates with the expression of 15-LO activity.
Considerable evidence suggests that the progression of
atherosclerosis includes events that are
immunologically mediated, lending potential
physiological relevance to these in vitro
observations.
Key Words: cellular activation • cytokines • human • monocytes • macrophages • LDL
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