Ionizing radiation stimulates secretion of pro-inflammatory cytokines: dose-response relationship, mechanisms and implications.
In previous studies we showed a marked increase in secretion of inflammatory cytokines TNFalpha and interleukin (IL)-1beta by mouse macrophages in response to different doses of ionizing radiation (IR). Here we show the stimulation of IL-12 and IL-18 secretion by mouse peritoneal macrophages after whole-body irradiation with exploration of the possible mechanisms and implications in cancer radiotherapy. Both low (0.075 Gy) and high (2 Gy) doses of IR were found to cause sustained stimulation of IL-12 and IL-18 secretion by mouse macrophages; this paralleled the activation of NF-kappaB as well as up-regulated expression of CD14 and TLR4-MD2 on the macrophage surface and MyD88 in the cytoplasm. The expression of CD14, TLR4-MD2 and MyD88 increased in a dose-dependent manner from radiation doses between 0.05 and 2 Gy. The secretion of IL-12 and IL-18 showed a dose-dependent increase from doses between 0.05 and 4 Gy. It is concluded that IR can stimulate the secretion of IL-12 and IL-18 presumably via activation of the Toll signaling pathway in macrophages. The potential harmful effect of repeated doses of radiation used in radiotherapy for certain cancers is discussed.
Shan
Yu-Xing
YX
MH Radiobiology Research Unit, Jilin University School of Public Health, 1163 Xinmin St., Changchun, 130021, China, drliusz@yahoo.com.
Jin
Shun-Zi
SZ
Liu
Xiao-Dong
XD
Liu
Yang
Y
Liu
Shu-Zheng
SZ
D000818:Animals; D019281:Dimerization; D004307:Dose-Response Relationship, Radiation; D018664:Interleukin-12 / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000032:analysis*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000032:analysis; D051996:Transcription Factor RelA / Q000378:metabolism; D014916:Whole-Body Irradiation
D020382:Interleukin-18; D018950:Lipopolysaccharide Receptors; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D052002:NF-kappa B p50 Subunit; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D018664:Interleukin-12