Interleukin-32 positively regulates radiation-induced vascular inflammation.
OBJECTIVE
To study the role of interleukin-32 (IL-32), a novel protein only detected in human tissues, in ionizing radiation (IR)-induced vascular inflammation.


METHODS
Irradiated (0-6 Gy) human umbilical vein endothelial cells treated with or without various agents--a cytosolic phospholipase A2 (cPLA2) inhibitor, a cyclooxygenase-2 (Cox-2) inhibitor, or lysophosphatidylcholines (LPCs)--were used to assess IL-32 expression by Northern blot analysis and quantitative reverse transcriptase-polymerase chain reaction. Expression of cell adhesion molecules and leukocyte adhesion to endothelial cells using human acute monocytic leukemia cell line (THP-1) cells was also analyzed.


RESULTS
Ionizing radiation dramatically increased IL-32 expression in vascular endothelial cells through multiple pathways. Ionizing radiation induced IL-32 expression through nuclear factor kappaB activation, through induction of cPLA2 and LPC, as well as induction of Cox-2 and subsequent conversion of arachidonic acid to prostacyclin. Conversely, blocking nuclear factor kappaB, cPLA2, and Cox-2 activity impaired IR-induced IL-32 expression. Importantly, IL-32 significantly enhanced IR-induced expression of vascular cell adhesion molecules and leukocyte adhesion on endothelial cells.


CONCLUSIONS
This study identifies IL-32 as a positive regulator in IR-induced vascular inflammation, and neutralization of IL-32 may be beneficial in protecting from IR-induced inflammation.
Kobayashi
Hanako
H
Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Yazlovitskaya
Eugenia M
EM
Lin
P Charles
PC
D015815:Cell Adhesion Molecules / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000528:radiation effects*; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D013381:Subtilisins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism / Q000528:radiation effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014657:Vasculitis / Q000209:etiology / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D052246:Cyclooxygenase 2 Inhibitors; C496971:IL32 protein, human; D007378:Interleukins; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D054513:Group IV Phospholipases A2; C099101:PCSK7 protein, human; D013381:Subtilisins