| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B Regulation Due to a Hyperactive IB Kinase1
,
,,,*
*
Department of Microbiology and Immunology, School of Medicine;
Department of Biology,
Lineberger Comprehensive Cancer Center, and
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599
Insulin-dependent diabetes mellitus (IDDM) is characterized by the
T cell-mediated destruction of insulin-producing 
cells.
Accordingly, APCs, such as macrophage, have also been shown to be
important in the disease process. However, the role(s) of dendritic
cells (DCs) that exhibit potent APC function remains undefined in IDDM.
Here we demonstrate that DCs derived from nonobese diabetic (NOD) mice,
a model for IDDM, are more sensitive to various forms of stimulation
compared with those from C57BL/6 and BALB/c mice, resulting in
increased IL-12 secretion. This property is a consequence of
hyperactivation of NF-
B, a transcription factor known to regulate
IL-12 gene expression. Specifically, NOD DCs exhibit persistent
hyperactivation of both IB kinase and NF-B in response to
stimuli, in addition to selective degradation of IB
. Transfection
of NOD DCs with a modified form of IB
significantly reduced IL-12
secretion, suggesting that hyperactivation of NF-B was in part
responsible for increased IL-12 production. An enhanced capacity of NOD
DCs to secrete IL-12 would be expected to contribute to the development
of pathogenic Th1 (Tc1) cells during the diabetogenic
response.
This article has been cited by other articles:
|
|
 |
|
  R. Tisch and B. Wang Role of Plasmacytoid Dendritic Cells in Type 1 Diabetes: Friend or Foe? Diabetes, January 1, 2009; 58(1): 12 - 13. [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Maier, S. K. Howlett, K. M. Rainbow, J. Clark, J. M. M. Howson, J. A. Todd, and L. S. Wicker NKG2D-RAE-1 Receptor-Ligand Variation Does Not Account for the NK Cell Defect in Nonobese Diabetic Mice J. Immunol., November 15, 2008; 181(10): 7073 - 7080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Marleau, K. L. Summers, and B. Singh Differential Contributions of APC Subsets to T Cell Activation in Nonobese Diabetic Mice J. Immunol., April 15, 2008; 180(8): 5235 - 5249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. U. A. Mollah, S. Pai, C. Moore, B. J. O'Sullivan, M. J. Harrison, J. Peng, K. Phillips, J. B. Prins, J. Cardinal, and R. Thomas Abnormal NF-{kappa}B Function Characterizes Human Type 1 Diabetes Dendritic Cells and Monocytes J. Immunol., March 1, 2008; 180(5): 3166 - 3175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Enzler, S. Gillessen, M. Dougan, J. P. Allison, D. Neuberg, D. A. Oble, M. Mihm, and G. Dranoff Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of {beta} cells Blood, August 1, 2007; 110(3): 954 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-M. Hu, H.-H. Lin, M.-T. Chiang, P.-F. Chang, and L.-Y. Chau Systemic Expression of Heme Oxygenase-1 Ameliorates Type 1 Diabetes in NOD Mice Diabetes, May 1, 2007; 56(5): 1240 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sen, M. A. Wallet, Z. Yi, Y. Huang, M. Henderson, C. E. Mathews, H. S. Earp, G. Matsushima, A. S. Baldwin Jr, and R. M. Tisch Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-{kappa}B activation in dendritic cells Blood, January 15, 2007; 109(2): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Carmody, Q. Ruan, H.-C. Liou, and Y. H. Chen Essential Roles of c-Rel in TLR-Induced IL-23 p19 Gene Expression in Dendritic Cells J. Immunol., January 1, 2007; 178(1): 186 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Alard, J. N. Manirarora, S. A. Parnell, J. L. Hudkins, S. L. Clark, and M. M. Kosiewicz Deficiency in NOD Antigen-Presenting Cell Function May Be Responsible for Suboptimal CD4+CD25+ T-Cell-Mediated Regulation and Type 1 Diabetes Development in NOD Mice. Diabetes, July 1, 2006; 55(7): 2098 - 2105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Noso, H. Ikegami, T. Fujisawa, Y. Kawabata, K. Asano, Y. Hiromine, M. Tsurumaru, S. Sugihara, I. Lee, E. Kawasaki, et al. Genetic Heterogeneity in Association of the SUMO4 M55V Variant With Susceptibility to Type 1 Diabetes Diabetes, December 1, 2005; 54(12): 3582 - 3586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Feili-Hariri, D. H. Falkner, and P. A. Morel Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine dendritic cell populations: implications for immunotherapy J. Leukoc. Biol., September 1, 2005; 78(3): 656 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Mathews, W. L. Suarez-Pinzon, J. J. Baust, K. Strynadka, E. H. Leiter, and A. Rabinovitch Mechanisms Underlying Resistance of Pancreatic Islets from ALR/Lt Mice to Cytokine-Induced Destruction J. Immunol., July 15, 2005; 175(2): 1248 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Corcoran, E. Feingold, J. Dominick, M. Wright, J. Harnaha, M. Trucco, N. Giannoukakis, and P. V. Benos Footer: A quantitative comparative genomics method for efficient recognition of cis-regulatory elements Genome Res., June 1, 2005; 15(6): 840 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kared, A. Masson, H. Adle-Biassette, J.-F. Bach, L. Chatenoud, and F. Zavala Treatment With Granulocyte Colony-Stimulating Factor Prevents Diabetes in NOD Mice by Recruiting Plasmacytoid Dendritic Cells and Functional CD4+CD25+ Regulatory T-Cells Diabetes, January 1, 2005; 54(1): 78 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Machen, J. Harnaha, R. Lakomy, A. Styche, M. Trucco, and N. Giannoukakis Antisense Oligonucleotides Down-Regulating Costimulation Confer Diabetes-Preventive Properties to Nonobese Diabetic Mouse Dendritic Cells J. Immunol., October 1, 2004; 173(7): 4331 - 4341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Koonce and E. K. Bikoff Dissecting MHC Class II Export, B Cell Maturation, and DM Stability Defects in Invariant Chain Mutant Mice J. Immunol., September 1, 2004; 173(5): 3271 - 3280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhattacharyya, P. Sen, M. Wallet, B. Long, A. S. Baldwin Jr, and R. Tisch Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of I{kappa}B kinase activity Blood, August 15, 2004; 104(4): 1100 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Bouma, W. K. Lam-Tse, A. F. Wierenga-Wolf, H. A. Drexhage, and M. A. Versnel Increased Serum Levels of MRP-8/14 in Type 1 Diabetes Induce an Increased Expression of CD11b and an Enhanced Adhesion of Circulating Monocytes to Fibronectin Diabetes, August 1, 2004; 53(8): 1979 - 1986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. B. Simpson, M. S. Mistry, R. A. Maki, W. Yang, D. A. Schwarz, E. B. Johnson, F. M. Lio, and D. G. Alleva Cutting Edge: Diabetes-Associated Quantitative Trait Locus, Idd4, Is Responsible for the IL-12p40 Overexpression Defect in Nonobese Diabetic (NOD) Mice J. Immunol., October 1, 2003; 171(7): 3333 - 3337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ma, S. Qian, X. Liang, L. Wang, J. E. Woodward, N. Giannoukakis, P. D. Robbins, S. Bertera, M. Trucco, J. J. Fung, et al. Prevention of Diabetes in NOD Mice by Administration of Dendritic Cells Deficient in Nuclear Transcription Factor-{kappa}B Activity Diabetes, August 1, 2003; 52(8): 1976 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Trembleau, G. Penna, S. Gregori, N. Giarratana, and L. Adorini IL-12 Administration Accelerates Autoimmune Diabetes in Both Wild-Type and IFN-{gamma}-Deficient Nonobese Diabetic Mice, Revealing Pathogenic and Protective Effects of IL-12-Induced IFN-{gamma} J. Immunol., June 1, 2003; 170(11): 5491 - 5501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Chang, S. Kim, J. Y. Kim, N. Cho, Y.-H. Kim, H. S. Kim, M.-K. Lee, K.-W. Kim, and M.-S. Lee Nuclear Factor {kappa}B Protects Pancreatic {beta}-Cells From Tumor Necrosis Factor-{alpha}-Mediated Apoptosis Diabetes, May 1, 2003; 52(5): 1169 - 1175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu and D. I. Beller Distinct Pathways for NF-{kappa}B Regulation Are Associated with Aberrant Macrophage IL-12 Production in Lupus- and Diabetes-Prone Mouse Strains J. Immunol., May 1, 2003; 170(9): 4489 - 4496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sen, S. Bhattacharyya, M. Wallet, C. P. Wong, B. Poligone, M. Sen, A. S. Baldwin Jr., and R. Tisch NF-{kappa}B Hyperactivation Has Differential Effects on the APC Function of Nonobese Diabetic Mouse Macrophages J. Immunol., February 15, 2003; 170(4): 1770 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Valero, M.-L. Baron, S. Guerin, S. Beliard, H. Lelouard, B. Kahn-Perles, B. Vialettes, C. Nguyen, J. Imbert, and P. Naquet A Defective NF-{kappa}B/RelB Pathway in Autoimmune-Prone New Zealand Black Mice Is Associated with Inefficient Expansion of Thymocyte and Dendritic Cells J. Immunol., July 1, 2002; 169(1): 185 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu and D. Beller Aberrant Production of IL-12 by Macrophages from Several Autoimmune-Prone Mouse Strains Is Characterized by Intrinsic and Unique Patterns of NF-{kappa}B Expression and Binding to the IL-12 p40 Promoter J. Immunol., July 1, 2002; 169(1): 581 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Steptoe, J. M. Ritchie, and L. C. Harrison Increased Generation of Dendritic Cells from Myeloid Progenitors in Autoimmune-Prone Nonobese Diabetic Mice J. Immunol., May 15, 2002; 168(10): 5032 - 5041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Poligone, D. J. Weaver Jr., P. Sen, A. S. Baldwin Jr., and R. Tisch Elevated NF-{kappa}B Activation in Nonobese Diabetic Mouse Dendritic Cells Results in Enhanced APC Function J. Immunol., January 1, 2002; 168(1): 188 - 196. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
