Soluble factor from tumor cells induces heme oxygenase-1 by a nitric oxide-independent mechanism in murine peritoneal macrophages |
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Authors: | Kim Sang-Wook Oh Hyun-Mee Kim Beom-Su Chung Hun-Taeg Han Weon-Cheol Kim Eun-Cheol Kim Tae-Hyeon Seo Geom-Seog Lyou June-Hyung Nah Yong-Ho Jung Jae-Chang Choi Suck-Chei Jun Chang-Duk |
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Affiliation: | Department of Digestive Research Unit, Wonkwang Medical Science Institute, Iksan, Chonbuk 570-749, Korea. |
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Abstract: | Tumor target-derived soluble secretary factor has been known to influence macrophage activation to induce nitric oxide (NO) production. Since heme oxygenase-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. |
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