help button home button Am J Pathol sign up for etoc
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gill, R. M.
Right arrow Articles by Hunt, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gill, R. M.
Right arrow Articles by Hunt, J. S.
(American Journal of Pathology. 2004;165:309-317.)
© 2004 American Society for Investigative Pathology

Soluble Receptor (DcR3) and Cellular Inhibitor of Apoptosis-2 (cIAP-2) Protect Human Cytotrophoblast Cells Against LIGHT-Mediated Apoptosis

Ryan M. Gill* and Joan S. Hunt*{dagger}

From the Departments of Pathology and Laboratory Medicine* and Anatomy and Cell Biology,{dagger} University of Kansas Medical Center, Kansas City, Kansas

LIGHT (tumor necrosis factor superfamily 14) is among the powerful apoptosis-inducing cytokines synthesized in human placentas. Here, we investigated mechanisms protecting cytotrophoblast (CTB) cells from LIGHT-mediated apoptosis. Viability assays and caspase-3 immunoblots using recombinant LIGHT were done to establish that CTB cells purified from term placentas resist LIGHT-induced apoptosis. Although the cells were also resistant to killing by another placental cytokine, interferon-{gamma} (IFN-{gamma}), a combination of the two induced apoptosis. Killing was prevented by DcR3-Fc fragment but not control human-Fc fragment, showing that apoptosis occurs via the LIGHT pathway and that soluble receptors provide protection. Next, two cellular inhibitors of apoptosis expressed in CTB cells, cellular inhibitor of apoptosis (cIAP)-1 and cIAP-2, were investigated for protection. Cellular IAP-1 was unchanged after stimulation with LIGHT whereas cIAP-2 mRNA and protein were elevated. The increase was abrogated by treating CTB cells with LIGHT + IFN-{gamma}, implying a central role for cIAP-2 in preventing LIGHT-mediated apoptosis and an ability of IFN-{gamma} to overcome cIAP-2 protection. Definitive evidence was provided in experiments that showed that cIAP-2 anti-sense morpholinos permit LIGHT to induce apoptosis in HT-29 cells. In summary, the data are consistent with the postulate that placental CTB cells are protected from LIGHT-mediated apoptosis by both soluble receptor, DcR3, and cIAP-2.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
D. L. Langat, D. A. Wheaton, J. S. Platt, T. Sifers, and J. S. Hunt
Signaling Pathways for B Cell-Activating Factor (BAFF) and a Proliferation-Inducing Ligand (APRIL) in Human Placenta
Am. J. Pathol., May 1, 2008; 172(5): 1303 - 1311.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
R T Kilani, M Mackova, S T Davidge, B Winkler-Lowen, N Demianczuk, and L J Guilbert
Endogenous tumor necrosis factor {alpha} mediates enhanced apoptosis of cultured villous trophoblasts from intrauterine growth-restricted placentae
Reproduction, January 1, 2007; 133(1): 257 - 264.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S. L. Straszewski-Chavez, V. M. Abrahams, and G. Mor
The Role of Apoptosis in the Regulation of Trophoblast Survival and Differentiation during Pregnancy
Endocr. Rev., December 1, 2005; 26(7): 877 - 897.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the American Society for Investigative Pathology.