Soluble factor from tumor cells induces heme oxygenase-1 by a nitric oxide-independent mechanism in murine peritoneal macrophages.
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.
Kim
Sang-Wook
SW
Department of Digestive Research Unit, Wonkwang Medical Science Institute, Iksan, Chonbuk 570-749, Korea.
Oh
Hyun-Mee
HM
Kim
Beom-Su
BS
Chung
Hun-Taeg
HT
Han
Weon-Cheol
WC
Kim
Eun-Cheol
EC
Kim
Tae-Hyeon
TH
Seo
Geom-Seog
GS
Lyou
June-Hyung
JH
Nah
Yong-Ho
YH
Jung
Jae-Chang
JC
Choi
Suck-Chei
SC
Jun
Chang-Duk
CD
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D004347:Drug Interactions; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D008565:Membrane Proteins; D009573:Nitrites; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse