PMID- 18755151 OWN - NLM STAT- MEDLINE DCOM- 20081027 LR - 20131121 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 375 IP - 4 DP - 2008 Oct 31 TI - Bone marrow stromal cells induce apoptosis of lymphoma cells in the presence of IFNgamma and TNF by producing nitric oxide. PG - 666-70 LID - 10.1016/j.bbrc.2008.08.077 [doi] AB - Bone marrow stromal cells (BMSCs) have been shown to promote the growth and survival of a wide variety of tumors. However, in the present study, we found that BMSCs induced apoptosis of lymphoma cells in the presence of INFgamma and TNF. IFNgamma and TNF dramatically induced the expression of inducible nitric oxide synthase (iNOS) by BMSCs in culture, and BMSCs generated from iNOS knockout mice did not induce apoptosis of lymphoma cells in the presence of IFNgamma and TNF. In addition, we found that IFNgamma and TNF also increased IL-6 expression by BMSCs, and anti-IL-6 further increased the killing of tumor cells by BMSCs. Taken together, our findings indicate that BMSCs induce apoptosis of lymphoma cells in the presence of IFNgamma and TNF, and that the proapoptotic effect of BMSCs is mediated by nitric oxide. Our findings suggest a possibility to harness this proapoptotic feature of BMSCs for the development of novel therapeutic strategy to eliminate tumor cells, especially tumor cells in bone marrow. FAU - Xu, Guangwu AU - Xu G AD - Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, 661 Hoes Lane, Piscataway, NJ 08854, USA. FAU - Zhang, Yingyu AU - Zhang Y FAU - Zhang, Liying AU - Zhang L FAU - Ren, Guangwen AU - Ren G FAU - Shi, Yufang AU - Shi Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080826 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) SB - IM MH - Animals MH - *Apoptosis MH - Bone Marrow Cells/*drug effects/enzymology MH - Cell Line, Tumor MH - Interferon-gamma/*pharmacology MH - Lymphoma/pathology/*therapy MH - Mice MH - Mice, Knockout MH - Nitric Oxide/*biosynthesis MH - Nitric Oxide Synthase Type II/genetics MH - Stromal Cells/drug effects/enzymology MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 2008/08/30 09:00 MHDA- 2008/10/28 09:00 CRDT- 2008/08/30 09:00 PHST- 2008/08/13 00:00 [received] PHST- 2008/08/15 00:00 [accepted] PHST- 2008/08/30 09:00 [pubmed] PHST- 2008/10/28 09:00 [medline] PHST- 2008/08/30 09:00 [entrez] AID - S0006-291X(08)01621-5 [pii] AID - 10.1016/j.bbrc.2008.08.077 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2008 Oct 31;375(4):666-70. doi: 10.1016/j.bbrc.2008.08.077. Epub 2008 Aug 26.