Production of IFN-gamma by TNF-alpha in Macrophages from Tumor Micro Environment; Significance in Angiogenic Switch Control

BACKGROUND: The role of macrophages in tumor angiogenesis is known to be the production of angiogenic cytokines and growth factors including TNF-alpha. Recently, macrophage also can produce the INF-gamma that is being studied to be involved in angiogenic inhibition. Thus, the importance of macrophages in tumor angiogenesis is might being an angiogenic switch. Thus, the hypothesis tested here is that TNF-alpha can modulate the INF-gamma production in the macrophages from tumor environment as a part of tumor angiogenic switch. METHODS: Macrophages in tumor environment were obtained from the peritoneal cavity of C57BL/6 mice injected with B16F10 melanoma cell line for 6 or 11 days. Mac1(+) -macrophages were purified using magnetic bead (MACs(TM); Milteny Biotech, Germany) and cultured with various concentrations of TNF-alpha for various time points at 37degreeC. The supernatants were analyzed for IFN-gamma or VEGF by ELISA kit (Endogen, Woburn, MA). RESULTS: Residential macrophages from the peritoneal cavity did not respond to LPS or TNF-alpha to produce INF-gamma. However, the cells from tumor environment produced IFN-gamma as well as VEGF and upregulated by the addition of LPS or TNF-alpha. RT-PCR analysis revealed the external TNF-alpha-induced IFN-gamma gene expression in the macrophages from tumor environment. CONCLUSION: The overall data suggest that the macrophages in tumor environment might have an important role not only in angiogenic signal but also in anti-angiogenic signal by producing related cytokines. And TNF-alpha might be a key cytokine in tumor angiogenic switch.

Allicin Reduces Adhesion Molecules and NO Production Induced by gamma irradiation in Human Endothelial Cells

BACKGROUND: Inflammation is a frequent reaction following therapeutic irradiation. Since the upregulation of adhesion molecules on endothelial cell surface is known to be associated with inflammation, the expression of adhesion molecules is an important therapeutic target. METHODS: Treatment of human umbilical endothelial cells (HUVECs) with gamma irradiation (gamma R) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Changes in the expression of these proteins on gamma irradiated HUVECs which had been treated previously with allicin were measured by ELISA. RESULTS: In the present study, we demonstrate that allicin inhibits the gamma R induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose-dependent manner. Allicin was also found to inhibit thegamma R induced production of nitric oxide (NO). CONCLUSION: These data suggest that allicin has a therapeutic potential for the treatment of various inflammatory disorders associated with increase numbers of endothelial leukocyte adhesion molecules.

Class Ii MHC and Viral Expression by Hematopoietic Progenitor Cells Infected with Friend Virus / 대한면역학회지

No abstract available.