Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Alleva, D. G.
Right arrow Articles by Beller, D. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alleva, D. G.
Right arrow Articles by Beller, D. I.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes, Vol 49, Issue 7 1106-1115, Copyright © 2000 by American Diabetes Association

ARTICLES

Aberrant macrophage cytokine production is a conserved feature among autoimmune-prone mouse strains: elevated interleukin (IL)-12 and an imbalance in tumor necrosis factor-alpha and IL-10 define a unique cytokine profile in macrophages from young nonobese diabetic mice

DG Alleva, RP Pavlovich, C Grant, SB Kaser and DI Beller
Evans Memorial Department of Clinical Research, Boston University Medical Center, Massachusetts, USA.

Cytokines derived from macrophages (Mo) play a critical role in the development of type 1 diabetes in the nonobese diabetic (NOD) mouse. Based on earlier findings from lupus-prone strains of inherent cytokine defects in Mo , NOD Mo were evaluated for intrinsically dysregulated cytokine production with the potential to initiate or exacerbate disease. Endotoxin-activated peritoneal Mo from young prediseased NOD mice produced interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha levels similar to those of Mo from a panel of control strains but reduced compared with the congenic diabetes-resistant NOR strain. IL-6 and IL-10 production were similar in NOD and NOR Mo, indicating that reduction in NOD IL-1 and TNF-alpha expression was selective. Nevertheless, the ratio of TNF-alpha and IL-10 production, a stringent index of normal Mo function, distinguished NOD from all normal strains. The most striking feature of NOD Mo, however, was their substantially elevated IL-12 production. This response was induced not only by endotoxin but also by bacillus Calmette-Guerin (BCG) and CD40 ligand and was associated with (and likely caused by) the enhanced and prolonged expression of p40 mRNA. Moreover, NOD Mo IL-12 expression appeared to be near maximally induced by lipopolysaccharide (LPS) alone, because it was only slightly enhanced by the addition of gamma-interferon, a stimulus that substantially elevated LPS-induced IL-12 production in Mo from normal strains. Accompanied by a unique profile of TNF-alpha and IL-10, the dramatic elevation of IL-12 expression by NOD Mo reflects intrinsic defects of the innate immune system with the potential to initiate and propagate the pathogenic autoreactive T-helper type 1 response characteristic of type 1 diabetes.
Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
M. McDuffie, N. A. Maybee, S. R. Keller, B. K. Stevens, J. C. Garmey, M. A. Morris, E. Kropf, C. Rival, K. Ma, J. D. Carter, et al.
Nonobese Diabetic (NOD) Mice Congenic for a Targeted Deletion of 12/15-Lipoxygenase Are Protected From Autoimmune Diabetes
Diabetes, January 1, 2008; 57(1): 199 - 208.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
W. Gurr, M. Shaw, Y. Li, and R. Sherwin
RegII Is a {beta}-Cell Protein and Autoantigen in Diabetes of NOD Mice
Diabetes, January 1, 2007; 56(1): 34 - 40.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
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]

Home page
 EndocrinologyHome page
Y. Wen, J. Gu, S.-L. Li, M. A. Reddy, R. Natarajan, and J. L. Nadler
Elevated Glucose and Diabetes Promote Interleukin-12 Cytokine Gene Expression in Mouse Macrophages
Endocrinology, May 1, 2006; 147(5): 2518 - 2525.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Falasca, V. Iadevaia, F. Ciccosanti, G. Melino, A. Serafino, and M. Piacentini
Transglutaminase Type II Is a Key Element in the Regulation of the Anti-Inflammatory Response Elicited by Apoptotic Cell Engulfment
J. Immunol., June 1, 2005; 174(11): 7330 - 7340.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S.-J. Zheng, S.-E. Lamhamedi-Cherradi, P. Wang, L. Xu, and Y. H. Chen
Tumor Suppressor p53 Inhibits Autoimmune Inflammation and Macrophage Function
Diabetes, May 1, 2005; 54(5): 1423 - 1428.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Nikolic, M. Bunk, H. A. Drexhage, and P. J. M. Leenen
Bone Marrow Precursors of Nonobese Diabetic Mice Develop into Defective Macrophage-Like Dendritic Cells In Vitro
J. Immunol., October 1, 2004; 173(7): 4342 - 4351.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Oikawa, A. Shimada, A. Kasuga, J. Morimoto, T. Osaki, H. Tahara, T. Miyazaki, F. Tashiro, E. Yamato, J.-i. Miyazaki, et al.
Systemic Administration of IL-18 Promotes Diabetes Development in Young Nonobese Diabetic Mice
J. Immunol., December 1, 2003; 171(11): 5865 - 5875.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
K. S. Goudy, B. R. Burkhardt, C. Wasserfall, S. Song, M. L. Campbell-Thompson, T. Brusko, M. A. Powers, M. J. Clare-Salzler, E. S. Sobel, T. M. Ellis, et al.
Systemic Overexpression of IL-10 Induces CD4+CD25+ Cell Populations In Vivo and Ameliorates Type 1 Diabetes in Nonobese Diabetic Mice in a Dose-Dependent Fashion
J. Immunol., September 1, 2003; 171(5): 2270 - 2278.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
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]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 DiabetesHome page
Y. C. Zhang, A. Pileggi, A. Agarwal, R. D. Molano, M. Powers, T. Brusko, C. Wasserfall, K. Goudy, E. Zahr, R. Poggioli, et al.
Adeno-Associated Virus-Mediated IL-10 Gene Therapy Inhibits Diabetes Recurrence in Syngeneic Islet Cell Transplantation of NOD Mice
Diabetes, March 1, 2003; 52(3): 708 - 716.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 DiabetesHome page
B. A. O'Brien, Y. Huang, X. Geng, J. P. Dutz, and D. T. Finegood
Phagocytosis of Apoptotic Cells by Macrophages From NOD Mice Is Reduced
Diabetes, August 1, 2002; 51(8): 2481 - 2488.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 J. Leukoc. Biol.Home page
S. B. Flohe, J. Bruggemann, C. Herder, C. Goebel, and H. Kolb
Enhanced proinflammatory response to endotoxin after priming of macrophages with lead ions
J. Leukoc. Biol., March 1, 2002; 71(3): 417 - 424.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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 page
 J. Immunol.Home page
D. J. Weaver Jr., B. Poligone, T. Bui, U. M. Abdel-Motal, A. S. Baldwin Jr., and R. Tisch
Dendritic Cells from Nonobese Diabetic Mice Exhibit a Defect in NF-{kappa}B Regulation Due to a Hyperactive I{kappa}B Kinase
J. Immunol., August 1, 2001; 167(3): 1461 - 1468.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
D. G. Alleva, E. B. Johnson, J. Wilson, D. I. Beller, and P. J. Conlon
SJL and NOD macrophages are uniquely characterized by genetically programmed, elevated expression of the IL-12(p40) gene, suggesting a conserved pathway for the induction of organ-specific autoimmunity
J. Leukoc. Biol., March 1, 2001; 69(3): 440 - 448.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2000 by the American Diabetes Association.