Induction of interleukin-1beta and interleukin-6 mRNA by low doses of ionizing radiation in macrophages.
We have previously reported the antimetastatic effects and augmentation of immune responses, which would be a mechanism of the antimetastatic effects, of 0.1 to 0.2 Gy total body irradiation. To elucidate the cellular mechanisms of the augmentation of immune response, we investigated the effects of low-dose irradiation on gene expression of interleukin-1beta (IL-1beta) and IL-6 using mouse peritoneal macrophages in vitro. Absolute mRNA quantification was carried out using competitive polymerase chain reaction. Gene expression of IL-1beta and IL-6 was increased 1 to 2 hr after 2.0 Gy irradiation and then decreased to below the basal expression level 4 hr after irradiation. Irradiation with 0.1 Gy increased IL-6 expression 2 hr after irradiation, but it did not affect IL-1beta expression. Downregulation of IL-1beta and IL-6 observed 4 hr after 2.0 Gy irradiation was not observed with 0.1 Gy irradiation. The protein kinase C (PKC) inhibitor H7 and the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor wortmannin inhibited induction of IL-1beta and IL-6 expression, which suggests that radiation-induced IL-1beta and IL-6 expression is achieved by PKC- and PI3-kinase-mediated signaling.
Hosoi
Y
Y
Department of Radiation Oncology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyoku, Tokyo 113-0033, Japan. hosoi@m.u-tokyo.ac.jp
Miyachi
H
H
Matsumoto
Y
Y
Enomoto
A
A
Nakagawa
K
K
Suzuki
N
N
Ono
T
T
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008264:Macrophages / Q000528:radiation effects*; D051379:Mice; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism*; D011839:Radiation, Ionizing; D015398:Signal Transduction; D013997:Time Factors; D000077191:Wortmannin
D000730:Androstadienes; D016207:Cytokines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D011493:Protein Kinase C; D000077191:Wortmannin