NF-κB Signaling Regulates Functional Expression of the MHC Class I-Related Neonatal Fc Receptor for IgG via Intronic Binding Sequences

作者: Xindong Liu , Lilin Ye , Gregory J. Christianson , Jun-Qi Yang , Derry C. Roopenian

DOI: 10.4049/JIMMUNOL.179.5.2999

关键词:

摘要: The neonatal Fc receptor for IgG (FcRn) functions to transport maternal a fetus or newborn and protect from degradation. Although FcRn is expressed in variety of tissues cell types, the extent which expression regulated by immunological inflammatory events remains unknown. Stimulation intestinal epithelial lines, macrophage-like THP-1, freshly isolated human monocytes with cytokine TNF-α rapidly up-regulated gene expression. In addition, TLR ligands LPS CpG oligodeoxynucleotide enhanced level THP-1 monocytes. Treatment TNF-stimulated cells NF-κB-specific inhibitor overexpression dominant negative mutant inhibitory NF-κB (IκBα; S32A/S36A) resulted down-regulation By using chromatin immunoprecipitation we identified three binding sequences within introns 2 4 gene. An EMSA confirmed p50/p50 and/or p65/p50 complex (s) bound intron 2- 4-derived oligonucleotides containing putative sequences, respectively. intronic combination promoter alone luciferase reporter response stimulation p65 p50. DNA looping interactions potentially occurred after between as shown chromosome conformation capture assay. Finally, stimulations across an Caco-2 monolayer. Together, these data provide first evidence that signaling via regulates function.

参考文章(54)
Zakaria Hmama, Devki Nandan, Laura Sly, Keith L. Knutson, Patricia Herrera-Velit, Neil E. Reiner, 1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex Journal of Experimental Medicine. ,vol. 190, pp. 1583- 1594 ,(1999) , 10.1084/JEM.190.11.1583
Xiaoping Zhu, Junmin Peng, Daohong Chen, Xindong Liu, Lilin Ye, Hideki Iijima, Kumar Kadavil, Wayne I. Lencer, Richard S. Blumberg, Calnexin and ERp57 Facilitate the Assembly of the Neonatal Fc Receptor for IgG with β2-Microglobulin in the Endoplasmic Reticulum Journal of Immunology. ,vol. 175, pp. 967- 976 ,(2005) , 10.4049/JIMMUNOL.175.2.967
Georgia D. Tomaras, Dalton A. Foster, Christine M. Burrer, Steven M. Taffet, ETS transcription factors regulate an enhancer activity in the third intron of TNF-alpha. Journal of Leukocyte Biology. ,vol. 66, pp. 183- 193 ,(1999) , 10.1002/JLB.66.1.183
Ning Li, Minglang Zhao, Julio Hilario-Vargas, Phillip Prisayanh, Simon Warren, Luis A Diaz, Derry C Roopenian, Zhi Liu, Complete FcRn dependence for intravenous Ig therapy in autoimmune skin blistering diseases Journal of Clinical Investigation. ,vol. 115, pp. 3440- 3450 ,(2005) , 10.1172/JCI24394
Shreeram Akilesh, Stefka Petkova, Thomas J. Sproule, Daniel J. Shaffer, Gregory J. Christianson, Derry Roopenian, The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease Journal of Clinical Investigation. ,vol. 113, pp. 1328- 1333 ,(2004) , 10.1172/JCI18838
Michael Karin, Yinon Ben-Neriah, Phosphorylation Meets Ubiquitination: The Control of NF-κB Activity Annual Review of Immunology. ,vol. 18, pp. 621- 663 ,(2000) , 10.1146/ANNUREV.IMMUNOL.18.1.621
HAYDEN MS, None, Signaling to NF-kappaB. Genes & Development. ,vol. 18, pp. 2195- 2224 ,(2004) , 10.1101/GAD.1228704
E Svenungsson, G-Z Fei, K Jensen-Urstad, U de Faire, A Hamsten, J Frostegård, TNF-α: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease Lupus. ,vol. 12, pp. 454- 461 ,(2003) , 10.1191/0961203303LU412OA
J DiDonato, F Mercurio, C Rosette, J Wu-Li, H Suyang, S Ghosh, M Karin, Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation. Molecular and Cellular Biology. ,vol. 16, pp. 1295- 1304 ,(1996) , 10.1128/MCB.16.4.1295
R. Martone, G. Euskirchen, P. Bertone, S. Hartman, T. E. Royce, N. M. Luscombe, J. L. Rinn, F. K. Nelson, P. Miller, M. Gerstein, S. Weissman, M. Snyder, Distribution of NF-κB-binding sites across human chromosome 22 Proceedings of the National Academy of Sciences of the United States of America. ,vol. 100, pp. 12247- 12252 ,(2003) , 10.1073/PNAS.2135255100