Gamma-irradiation-induced intercellular adhesion molecule-1 (ICAM-1) expression is associated with catalase: activation of Ap-1 and JNK.
The ionizing radiation used in cancer therapy frequently produces damage to normal tissues and induces complex responses, including inflammation. The upregulation of the intercellular adhesion molecule-1 (ICAM-1) in response to numerous inducing factors is associated with inflammation. Therefore, this study examined the molecular mechanisms responsible for ICAM-1 expression induced by gamma-irradiation (gammaIR). ICAM-1 mRNA and cell surface expression were induced in A549 human lung epithelial cells after exposing them to gammaIR. Catalase expression and activity were also increased in gammaIR-treated cells. Treatment of the gammaIR-treated cells with catalase resulted in a significant increase in the ICAM-1 cell surface expression level. The catalase inhibitor 3-amino-1,2,4-triazole (AT) reduced the level of ICAM-1. Electrophoretic mobility shift assay (EMSA) analysis showed that activating protein 1 (AP-1) was activated by gammaIR, whereas NF-kappaB was not. Specific Jun N-terminal kinase (JNK) inhibition attenuated the upregulation of gammaIR stimulated ICAM-1. Western blot analysis revealed a marked elevation in activation of JNK. In addition, pretreatment with AT resulted in a decrease in the level of JNK phosphorylation and AP-1 activation. Overall, data suggest that induction of ICAM-1 expression by gammaIR is associated with catalase. Furthermore, catalase, JNKs, and AP-1 activation induce ICAM-1 upregulation through a sequential process.
Son
Eun-Wha
EW
Department of Pharmacognosy and Material Development, Kangwon National University, Samcheok City, Gangwon-do, Republic of Korea.
Rhee
Dong-Kwon
DK
Pyo
Suhkneung
S
D002374:Catalase / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism* / Q000528:radiation effects*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011832:Radiation Injuries / Q000503:physiopathology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1; D002374:Catalase; D048670:MAP Kinase Kinase 4