Received 1 December 2008; received in revised form 19 February 2009; accepted 1 April 2009.
Purpose
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 and Materials
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 κB 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 κB, 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.
Conclusion
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.
∗Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN
†Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN
‡Department of Cell and Development Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN
Reprint requests to: P. Charles Lin, Ph.D., Department of Radiation Oncology, Vanderbilt University Medical Center, 712 PRB, 2220 Pierce Ave., Nashville, TN 37232. Tel: (615) 936-1749; Fax: (615) 936-1872
This work was supported in part by National Institutes of Health Grants CA108856, NS45888, and AR053718 (to P.C.L.), a training grant (5T32CA093240) to H.K., and a grant from Elsa U. Pardee Foundation to E.M.Y.
ABSTRACT