HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grehan, J. F. Articles by Dalmasso, A. P. Search for Related Content PubMed PubMed Citation Articles by Grehan, J. F. Articles by Dalmasso, A. P.

IL-4 and IL-13 Induce Protection of Porcine Endothelial Cells from Killing by Human Complement and from Apoptosis through Activation of a Phosphatidylinositide 3-Kinase/Akt Pathway¹

Departments of Surgery and Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, MN 55455

Vascular endothelial cells (EC) perform critical functions that require a balance of cell survival and cell death. EC death by apoptosis and EC activation and injury by the membrane attack complex of complement are important mechanisms in atherosclerosis and organ graft rejection. Although the effects of various cytokines on EC apoptosis have been studied, little is known about their effects on complement-mediated EC injury. Therefore, we studied the abilities of various cytokines to induce protection of porcine aortic EC against apoptosis and killing by human complement, a model of pig-to-human xenotransplantation. We found that porcine EC incubated with IL-4 or IL-13, but not with IL-10 or IL-11, became protected from killing by complement and apoptosis induced by TNF- plus cycloheximide. Maximal protection required 10 ng/ml IL-4 or IL-13, developed progressively from 12 to 72 h of incubation, and lasted 48–72 h after cytokine removal. Protection from complement was not associated with reduced complement activation, C9 binding, or changes in CD59 expression. Inhibition of PI3K prevented development of protection; however, inhibition of p38 MAPK or p42/44 MAPK had no effect. IL-4 and IL-13 induced rapid phosphorylation of Akt. Although protection was inhibited by an Akt inhibitor and a dominant negative Akt mutant transduced into EC, it was induced by transduction of EC with the constitutively active Akt variant, myristylated Akt. We conclude that IL-4 and IL-13 can induce protection of porcine EC against killing by apoptosis and human complement through activation of the PI3K/Akt signaling pathway.

This article has been cited by other articles:

				M. L. Slattery and F.A. Fitzpatrick Convergence of Hormones, Inflammation, and Energy-Related Factors: A Novel Pathway of Cancer Etiology Cancer Prevention Research, November 1, 2009; 2(11): 922 - 930. [Abstract] [Full Text] [PDF]

				L. H. Wei, Y. Yang, G. Wu, and L. J. Ignarro IL-4 and IL-13 upregulate ornithine decarboxylase expression by PI3K and MAP kinase pathways in vascular smooth muscle cells Am J Physiol Cell Physiol, May 1, 2008; 294(5): C1198 - C1205. [Abstract] [Full Text] [PDF]

				M. F. Denny, S. Thacker, H. Mehta, E. C. Somers, T. Dodick, F. J. Barrat, W. J. McCune, and M. J. Kaplan Interferon-{alpha} promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis Blood, October 15, 2007; 110(8): 2907 - 2915. [Abstract] [Full Text] [PDF]

				S. M. Black, J. F. Grehan, A. L. Rivard, B. A. Benson, A. E. Wahner, A. E. Koch, B. K. Levay-Young, and A. P. Dalmasso Porcine Endothelial Cells and Iliac Arteries Transduced with AdenoIL-4 Are Intrinsically Protected, through Akt Activation, against Immediate Injury Caused by Human Complement J. Immunol., November 15, 2006; 177(10): 7355 - 7363. [Abstract] [Full Text] [PDF]