This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mezosi, E. Articles by Baker, J. R. Search for Related Content PubMed PubMed Citation Articles by Mezosi, E. Articles by Baker, J. R., Jr.

Interleukin-1ß and Tumor Necrosis Factor (TNF)- Sensitize Human Thyroid Epithelial Cells to TNF-Related Apoptosis-Inducing Ligand-Induced Apoptosis through Increases in Procaspase-7 and Bid, and the Down-Regulation of p44/42 Mitogen-Activated Protein Kinase Activity

Center for Biologic Nanotechnology (J.R.B.) and the Departments of Medicine (E.M., S.H.W., S.U., J.D.B., J.R.B.), Physiology (L.B.), and Surgery (P.G.G., N.W.T.), University of Michigan Medical Center, Ann Arbor, Michigan 48109

Address all correspondence and requests for reprints to: James R. Baker, Jr., M.D., University of Michigan Medical Center, 9220 MSRB III, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-0648. E-mail: jbakerjr{at}umich.edu.

Primary thyroid cells are resistant to TNF-related apoptosis-inducing ligand (TRAIL). Previously we showed that the combination of IL-1ß and TNF facilitated TRAIL-mediated apoptosis in these cells and enhanced cell surface expression of TRAIL receptors. The aim of this study was to further characterize the mechanism by which these cytokines sensitized primary thyroid cells to TRAIL-mediated apoptosis. IL-1ß and TNF increased the concentrations of procaspase-7 and Bid. In contrast, the p44/42 MAPK (Erk) pathway was active in thyroid cells and this activity was significantly decreased after exposure to IL-1ß/TNF. A MAPK kinase inhibitor (U0126) could enhance the cytokine-induced sensitization of thyroid cells to TRAIL, reinforcing the inhibitory role of Erk on TRAIL signaling. In conclusion, IL-1ß/TNF treatment sensitizes human thyroid cells to TRAIL-mediated apoptosis through increased surface expression of TRAIL receptors, increased expression of procaspase-7 and Bid, and the inhibition of p44/42 MAPK (Erk) pathway.

This work was supported by National Institutes of Health Grants R01 A137141 and P60DK20572.

Abbreviations: cFLIP, Cellular FADD-like IL-1ß converting enzyme inhibitory protein; DcR, decoy receptor; DR, death receptor; IAP, inhibitor of apoptosis protein; IFN, interferon; MEK, MAPK kinase; NF-B, nuclear factor B; NP-40, Nonidet-P40; p90RSK, ribosomal S6 kinase; TEC, thyroid epithelial cell; TRAIL, TNF-related apoptosis-inducing ligand.

This article has been cited by other articles:

				S. H. Wang, G.-H. Chen, Y. Fan, M. Van Antwerp, and J. R. Baker Jr. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Inhibits Experimental Autoimmune Thyroiditis by the Expansion of CD4+CD25+ Regulatory T Cells Endocrinology, April 1, 2009; 150(4): 2000 - 2007. [Abstract] [Full Text] [PDF]

				L. A. O'Brien, M. A. Richardson, S. F. Mehrbod, D. T. Berg, B. Gerlitz, A. Gupta, and B. W. Grinnell Activated Protein C Decreases Tumor Necrosis Factor Related Apoptosis-Inducing Ligand by an EPCR- Independent Mechanism Involving Egr-1/Erk-1/2 Activation Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2634 - 2641. [Abstract] [Full Text] [PDF]

				Z.-X. Du, H.-Q. Wang, H.-Y. Zhang, and D.-X. Gao Involvement of Glyceraldehyde-3-Phosphate Dehydrogenase in Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Mediated Death of Thyroid Cancer Cells Endocrinology, September 1, 2007; 148(9): 4352 - 4361. [Abstract] [Full Text] [PDF]

				G. Chiappetta, M. Ammirante, A. Basile, A. Rosati, M. Festa, M. Monaco, E. Vuttariello, R. Pasquinelli, C. Arra, M. Zerilli, et al. The Antiapoptotic Protein BAG3 Is Expressed in Thyroid Carcinomas and Modulates Apoptosis Mediated by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1159 - 1163. [Abstract] [Full Text] [PDF]

				A.-C. Gerard, M. Boucquey, M.-F. van den Hove, and I. M. Colin Expression of TPO and ThOXs in human thyrocytes is downregulated by IL-1{alpha}/IFN-{gamma}, an effect partially mediated by nitric oxide Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E242 - E253. [Abstract] [Full Text] [PDF]

				E. Mezosi, S. H. Wang, S. Utsugi, L. Bajnok, J. D. Bretz, P. G. Gauger, N. W. Thompson, and J. R. Baker Jr. Induction and Regulation of Fas-Mediated Apoptosis in Human Thyroid Epithelial Cells Mol. Endocrinol., March 1, 2005; 19(3): 804 - 811. [Abstract] [Full Text] [PDF]