Radiation-Induced Interleukin-6 Expression Through MAPK/p38/NF-kappaB Signaling Pathway and the Resultant Antiapoptotic Effect on Endothelial Cells Through Mcl-1 Expression With sIL6-Ralpha
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (China)
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan (China)
Purpose: To investigate the mechanism of interleukin-6 (IL-6) activity induced by ionizing radiation. Methods and Materials: Human umbilical vascular endothelial cells (HUVECs) 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 oligodeoxynucleotides, and Western blotting were conducted to investigate the signal transduction pathway. Recombinant soluble human IL-6 receptor alpha-chain (sIL6-Ralpha) 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-kappaB (NF-kappaB) activation, prevented both the transcriptional and translational regulation of radiation-induced IL-6 expression. The addition of sIL6-Ralpha rescued HUVECs from radiation-induced death in an IL-6 concentratio-dependent manner. The antiapoptotic effect of combined sIL6-Ralpha 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-kappaB/IkappaB (inhibitor of NF-kappaB) complex activation. In the presence of sIL6-Ralpha, radiation-induced IL-6 expression acts through Mcl-1 expression to rescue endothelial cells from radiation-induced death.
- OSTI ID:
- 21367569
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 75, Issue 5; Other Information: DOI: 10.1016/j.ijrobp.2009.08.034; PII: S0360-3016(09)02981-2; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BIOLOGICAL RADIATION EFFECTS
ENDOTHELIUM
IONIZING RADIATIONS
POLYMERASE CHAIN REACTION
PROMOTERS
RECEPTORS
ANIMAL TISSUES
BIOLOGICAL EFFECTS
BODY
GENE AMPLIFICATION
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
PROTEINS
RADIATION EFFECTS
RADIATIONS