Radiation-Induced Interleukin-6 Expression through Mapk/P38/Nf-Kappa B Signaling Pathway and the Resultant Antiapoptotic Effect on Endothelial Cells through Mcl-1 Expression with Sil6-R Alpha
Resource
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS v.75 n.5 pp.1553-1561
Journal
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
Journal Volume
v.75
Journal Issue
n.5
Pages
1553-1561
Date Issued
2009
Date
2009
Author(s)
CHOU, CHIA-HUNG
CHEN, SHEE-UAN
CHENG, JASON CHIA-HSIEN
Abstract
To investigate the mechanism of interleukin-6 (IL-6) activity induced by ionizing radiation. Methods and Materials: Human umbilical vascular endothelial cells ( RUVECs) were irradiated with different doses to induce IL-6. The IL-6 promoter assay and reverse transcriptase- polymerase chain reaction (RT-PCR) were used to examine transcriptional regulation. Specific chemical inhibitors, decoy double-stranded oligodeoxy-nucleotides , and Western blotting were conducted to investigate the signal transduction pathway. Recombinant soluble human IL-6 receptor alpha-chain (sIL6-R alpha) and specific small interfering RNA were used to evaluate the biologic function of radiation-induced IL-6. Results: Four grays of radiation induced the highest level of IL-6 protein. The promoter assay and RT-PCR data revealed that the induction of IL-6 was mediated through transcriptional regulation. The p38 inhibitor SB203580, by blocking nuclear factor-kappa B (NF- kappa B) activation, prevented both the transcriptional and translational regulation of radiation-induced IL-6 expression. The addition of sIL6-R alpha rescued HUVECs from radiation- induced death in an IL-6 concentratio-dependent manner. The antiapoptotic effect of combined sIL6-R alpha and radiation-induced IL-6 was inhibited by mcl-1-specific small interfering RNA. Conclusion: Radiation transcriptionally induces IL-6 expression in endothelial cells through mitogen-activated protein kinase/p38-mediated NF-kappa B/I kappa B ( inhibitor of NF-kappa B) complex activation. In the presence of sIL6-R alpha, radiation- induced IL-6 expression acts through Mcl-1 expression to rescue endothelial cells from radiation-induced death.
Subjects
Interleukin-6
Radiation
Endothelial cell
Resistance