Exp Mol Med.
2003 Feb;35(1):53-59.
Soluble factor from tumor cells induces heme oxygenase-1 by a nitric oxide-independent mechanism in murine peritoneal macrophages
- Affiliations
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- 1Department of Digestive Research Unit Wonkwang Medical Science Institute, Korea.
- 2Genome Research Center for Immune Disorders, Korea.
- 3Department of Microbiology and Immunology Wonkwang University School of Medicine, Korea.
- 4Department of Pathology Wonkwang University School of Dentistry Iksan, Chonbuk 570-749, Korea.
- 5Department of Biology Kyungpook National University, Daegu 702-701, Korea.
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.
Keyword
MeSH Terms
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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
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