title: Irradiated U937 cells trigger inflammatory bystander responses in human umbilical vein endothelial cells through the p38 pathway.
abstract: Radiation-induced bystander effects are a well-known phenomenon that are observed when treating cancer and other diseases after radiotherapy, and even after occupational exposure to radiation. However, little is known about the crosstalk between irradiated macrophages and endothelial cells that line the circulatory system, which may play a role in the development of atherosclerosis. In the current study, we found that the expression of inducible nitric oxide synthase (iNOS) and the intracellular level of nitric oxide (NO) in gamma-irradiated U937 macrophage cells were significantly increased. When human umbilical vein endothelial cells (HUVECs) were co-cultured with gamma-irradiated U937 cells, additional micronuclei (MN) and apoptosis were induced so that the plating efficiency of the bystander HUVECs decreased and P38 was overexpressed in the bystander HUVECs cells. In addition, the contents of vascular cell adhesion molecule 1 (VCAM-1) and the activities of matrix metalloproteinase-9 (MMP-9) in the culture medium of bystander HUVECs were increased. Furthermore, during cell co-culture the adhesive ability of irradiated U937 cells to the bystander HUVECs increased. When U937 cells were treated with 500 μM S-methylisothiourea sulfate (SMT) (iNOS inhibitor) before irradiation, and HUVECs were treated with 10 μM SB203580 (p38 inhibitor) before cell co-culture or treated with 20 μM c-PTIO (NO scavenger) in the co-culture medium, the bystander micronuclei and the amounts of VCAM-1 and MMP-9 in the medium of bystander HUVECs were diminished, and the ability of irradiated U937 cells adhering to HUVECs was also reduced, while the plating efficiency of bystander HUVECs partially recovered. These results demonstrated that irradiated U937 cells appear to release nitric oxide and thereby further trigger apoptosis and inflammatory responses in the bystander HUVECs through a p38-dependent pathway.
authors: a  Institute of Radiation Medicine, Fudan University, Shanghai 200032, China; and.
authors: Linlin
authors: L
authors: Xiao
authors: Weili
authors: W
authors: Liu
authors: Jitao
authors: J
authors: Li
authors: Yuexia
authors: Y
authors: Xie
authors: Mingyuan
authors: M
authors: He
authors: Jiamei
authors: J
authors: Fu
authors: Wensen
authors: W
authors: Jin
authors: Chunlin
authors: C
authors: Shao
mesh_terms: D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology; D001565:Benzoates / Q000494:pharmacology; D024201:Bystander Effect / Q000528:radiation effects*; D018920:Coculture Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000528:radiation effects*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D009569:Nitric Oxide / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001565:Benzoates; D007093:Imidazoles; D011725:Pyridines; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D007550:Isothiuronium; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases; C027744:S-methylisothiopseudouronium; C093642:SB 203580