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.
Subject(s)
Animals , Humans , Mice , Antineoplastic Agents/pharmacology , Urinary Bladder Neoplasms/metabolism , Cell Line , Drug Interactions , Gene Expression Regulation, Enzymologic/drug effects , Heme Oxygenase (Decyclizing)/analysis , Interferon-gamma/pharmacology , Macrophage Activation/drug effects , Macrophages, Peritoneal/metabolism , Mice, Inbred C57BL , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/genetics , Nitrites/analysis , Tumor Cells, CulturedABSTRACT
Benign tumors of the extrahepatic bile duct are rare. They occur mostly in the common bile duct. Among them, papillomas and adenomas are most common. We experienced a case of villous adenomas in the common bile duct and also in the cystic duct. The ultrasound and the CT scan of the abdomen revealed markedly dilated common bile duct, subtle filling defect, and irregular mass narrowing the lumen of the common bile duct. The cholangiogram demonstrated movable, feathery, and marginated papillary mass with tumors, a broad base, and biopsy of this mass was done through the PTBD. The biopsy specimen showed villous adenoma. Even though it was diagnosed as benign, cholecystectomy and excision with Roux-en-Y hepaticojejunostomy was performed because of the high incidence of recurrences and malignant potential.