Soluble factor from tumor cells induces heme oxygenase-1 by a nitric oxide-independent mechanism in murine peritoneal macrophages.
- Author:
Sang Wook KIM
1
;
Hyun Mee OH
;
Beom Su KIM
;
Hun Taeg CHUNG
;
Weon Cheol HAN
;
Eun Cheol KIM
;
Tae Hyeon KIM
;
Geom Seog SEO
;
June Hyung LYOU
;
Yong Ho NAH
;
Jae Chang JUNG
;
Suck Chei CHOI
;
Chang Duk JUN
Author Information
1. Department of Digestive Research Unit Wonkwang Medical Science Institute, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
heme oxygenase;
interferon type II;
ma-crophages;
neoplasms;
nitric oxide;
nitric-oxide syn-thase
- MeSH:
Animals;
Antineoplastic Agents/pharmacology;
Bladder Neoplasms/metabolism/pathology;
Cell Line;
Drug Interactions;
Gene Expression Regulation, Enzymologic/drug effects;
Heme Oxygenase (Decyclizing)/analysis/*genetics;
Human;
Interferon Type II/pharmacology;
Macrophage Activation/drug effects;
Macrophages, Peritoneal/*metabolism;
Mice;
Mice, Inbred C57BL;
Nitric Oxide/biosynthesis/*metabolism;
Nitric-Oxide Synthase/genetics/metabolism;
Nitrites/analysis;
Tumor Cells, Cultured
- From:Experimental & Molecular Medicine
2003;35(1):53-59
- CountryRepublic of Korea
- Language:English
-
Abstract:
Tumor target-derived soluble secretary factor has been known to influence macrophage activation to induce nitric oxide (NO) production. Since heme oxigenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress, we questioned whether soluble factor from tumor cells induces HO-1 through NO-dependent mechanism in macrophages. We designated this factor as a tumor-derived macrophage-activating factor (TMAF), because of its ability to activate macrophages to induce iNOS. Although TMAF alone showed modest activity, TMAF in combination with IFN-gamma significantly induced iNOS expression and NO synthesis. Simultaneously, TMAF induced HO-1 and this induction was slightly augmented by IFN-gamma. Surprisingly, however, induction of HO-1 by TMAF was not inhibited by the treatment with the highly selective iNOS inhibitor, 1400 W, indicating that TMAF induces the HO-1 enzyme by a NO-independent mechanism. While rIFN-gamma alone induced iNOS, it had no effect on HO-1 induction by itself. Collectively, the current study reveals that soluble factor from tumor target cells induces HO-1 enzyme in macrophages. However, overall biological significance of this phenomenon remains to be determined.
