You are not currently logged in.
Access your personal account or get JSTOR access through your library or other institution:
If You Use a Screen ReaderThis content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
IL-32-Dependent Effects of IL-1β on Endothelial Cell Functions
Claudia A. Nold-Petry, Marcel F. Nold, Jarod A. Zepp, Soo-Hyun Kim, Norbert F. Voelkel and Charles A. Dinarello
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 10 (Mar. 10, 2009), pp. 3883-3888
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/40428469
Page Count: 6
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Preview not available
Increasing evidence demonstrates that interleukin (IL)-32 is a proinflammatory cytokine, inducing IL-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and chemokines via nuclear factor (NF)-kB, p38 mitogen-activated protein kinase (MAPK), and activating protein (AP)-1 activation. Here we report that IL-32 is expressed and is also functional in human vascular endothelial cells (EC) of various origins. Compared with primary blood monocytes, high levels of IL-32 are constitutively produced in human umbilical vein EC (HUVEC), aortic macrovascular EC, and cardiac as well as pulmonary microvascular EC. At concentrations as low as 0.1 ng/ml, IL-1β stimulated IL-32 up to 15-fold over constitutive levels, whereas 10 ng/ml of TNFα or 100 ng/ml of lipopolysaccharide (LPS) were required to induce similar quantities of IL-32. IL-1β-induced IL-32 was reduced by inhibition of the IKB kinase-β/NF-kB and ERK pathways. In addition to IL-1β, pro-coagulant concentrations of thrombin or fresh platelets increased IL-32 protein up to 6-fold. IL-1β and thrombin induced an isoformswitch in steady-state mRNA levels from IL-32α/γ to β/ε. Adult EC responded in a similar fashion. To prove functionality, we silenced endogenous IL-32 with siRNA, decreasing intracellular IL-32 protein levels by 86%. The knockdown of IL-32 resulted in reduction of constitutive as well as IL-1β-induced intercellular adhesion molecule-1 (ICAM-1) (of 55% and 54%, respectively), IL-1α (of 62% and 43%), IL-6 (of 53% and 43%), and IL-8 (of 46% and 42%). In contrast the anti-inflammatory/anti-coagulant CD141/thrombomodulin increased markedly when IL-32 was silenced. This study introduces IL-32 as a critical regulator of endothelial function, expanding the properties of this cytokine relevant to coagulation, endothelial inflammation, and atherosclerosis.
Proceedings of the National Academy of Sciences of the United States of America © 2009 National Academy of Sciences