title: Low-dose gamma-irradiation inhibits IL-6 secretion from human lung fibroblasts that promotes bronchial epithelial cell transformation by cigarette-smoke carcinogen.
abstract: Despite decades of research in defining the health effects of  low-dose (<100 mGy) ionizing photon radiation (LDR), the relationship between LDR and human cancer risk remains elusive. Because chemical carcinogens modify the tumor microenvironment, which is critical for cancer development, we investigated the role and mechanism of LDR in modulating the response of stromal cells to chemical carcinogen-induced lung cancer development. Secretion of proinflammatory cytokines such as interleukin-6 (IL-6), CXCL1 and CXCL5 from human lung fibroblasts was induced by cigarette-smoke carcinogen benzo[a]pyrene diol epoxide (BPDE), which was inhibited by a single dose of LDR. The activation of NF-κB, which is important for BPDE-induced IL-6 secretion, was also effectively suppressed by LDR. In addition, conditioned media from BPDE-treated fibroblasts activated STAT3 in the immortalized normal human bronchial epithelial cell line Beas-2B, which was blocked with an IL-6 neutralizing antibody. Conditioned medium from LDR-primed and BPDE-treated fibroblast showed diminished capacity in activating STAT3. Furthermore, IL-6 enhanced BPDE-induced Beas-2B cell transformation in vitro. These results suggest that LDR inhibits cigarette smoke-induced lung carcinogenesis by suppressing secretion of cytokines such as IL-6 from fibroblasts in lung tumor-prone microenvironment.
authors.affiliation: Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr., SE Albuquerque, NM 87108, USA.
authors.forename: Wenshu
authors.initials: W
authors.lastname: Chen
authors.forename: Xiuling
authors.initials: X
authors.lastname: Xu
authors.forename: Lang
authors.initials: L
authors.lastname: Bai
authors.forename: Mabel T
authors.initials: MT
authors.lastname: Padilla
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Gott
authors.forename: Shuguang
authors.initials: S
authors.lastname: Leng
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Tellez
authors.forename: Julie A
authors.initials: JA
authors.lastname: Wilder
authors.forename: Steven A
authors.initials: SA
authors.lastname: Belinsky
authors.forename: Bobby R
authors.initials: BR
authors.lastname: Scott
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D004307:Dose-Response Relationship, Radiation; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000528:radiation effects*; D008168:Lung / Q000378:metabolism / Q000528:radiation effects*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D012906:Smoke; D014026:Nicotiana
chemical_list: D002273:Carcinogens; D015850:Interleukin-6; D016328:NF-kappa B; D012906:Smoke; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide