title: The crosstalk between α-irradiated Beas-2B cells and its bystander U937 cells through MAPK and NF-κB signaling pathways.
abstract: Although accumulated evidence suggests that α-particle irradiation induced bystander effect may relevant to lung injury and cancer risk assessment, the exact mechanisms are not yet elucidated. In the present study, a cell co-culture system was used to investigate the interaction between α-particle irradiated human bronchial epithelial cells (Beas-2B) and its bystander macrophage U937 cells. It was found that the cell co-culture amplified the detrimental effects of α-irradiation including cell viability decrease and apoptosis promotion on both irradiated cells and bystander cells in a feedback loop which was closely relevant to the activation of MAPK and NF-κB pathways in the bystander U937 cells. When these two pathways in U937 cells were disturbed by special pharmacological inhibitors before cell co-culture, it was found that a NF-κB inhibitor of BAY 11-7082 further enhanced the proliferation inhibition and apoptosis induction in bystander U937 cells, but MAPK inhibitors of SP600125 and SB203580 protected cells from viability loss and apoptosis and U0126 presented more beneficial effect on cell protection. For α-irradiated epithelial cells, the activation of NF-κB and MAPK pathways in U937 cells participated in detrimental cellular responses since the above inhibitors could largely attenuate cell viability loss and apoptosis of irradiated cells. Our results demonstrated that there are bilateral bystander responses between irradiated lung epithelial cells and macrophages through MAPK and NF-κB signaling pathways, which accounts for the enhancement of α-irradiation induced damage.
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Fu
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Dexiao
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Tu
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China. Electronic address: clshao@shmu.edu.cn.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D000512:Alpha Particles; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001980:Bronchi / Q000166:cytology; D024201:Bystander Effect / Q000528:radiation effects*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D025461:Feedback, Physiological / Q000528:radiation effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000528:radiation effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D011725:Pyridines / Q000494:pharmacology; D020298:U937 Cells / Q000528:radiation effects*
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; C432165:pyrazolanthrone; C093642:SB 203580
keywords: Bilateral bystander responses; MAPKs; NF-κB; α-Particle irradiation