Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monocytes

Mollah, Zia U.A., Pai, Saparna, Craig Moore, O'Sullivan, Brendan J., Harrison, Matthew J., Peng, Judy, Phillips, Karen, Prins, Johannes B., Cardinal, John and Thomas, Ranjeny (2008) Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monocytes. Journal of Immunology, 180 5: 3166-3175.

Author Mollah, Zia U.A.
Pai, Saparna
Craig Moore
O'Sullivan, Brendan J.
Harrison, Matthew J.
Peng, Judy
Phillips, Karen
Prins, Johannes B.
Cardinal, John
Thomas, Ranjeny
Title Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monocytes
Journal name Journal of Immunology  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2008-03-01
Sub-type Article
Year available 2008
Volume number 180
Issue number 5
ISSN 0022-1767;1550-6606
Start page 3166
End page 3175
Total pages 10
Place of publication Bethesda, M.D, United States
Publisher The American Association of Immunologists
Collection year 2009
Language eng
Subject 920104 Diabetes
110703 Autoimmunity
Abstract Dendritic cell (DC) differentiation is abnormal in type 1 diabetes mellitus (T1DM). However, the nature of the relationship between this abnormality and disease pathogenesis is unknown. We studied the LPS response in monocytes and monocyte-derived DCs isolated from T1DM patients and from non-T1DM controls. In T1DM patients, late LPS-mediated nuclear DNA binding by RelA, p50, c-Rel, and RelB was impaired as compared with type 2 DM, rheumatoid arthritis, and healthy subjects, associated with impaired DC CD40 and MHC class I induction but normal cytokine production. In TIDM monocytes, RelA and RelB were constitutively activated, and the src homology 2 domain-containing protein tyrosine phosphatase (SHP-1), a negative regulator of NF-{kappa}B, was overexpressed. Addition of sodium stibogluconate, a SHP-1 inhibitor, to DCs differentiating from monocyte precursors restored their capacity to respond to LPS in ~60% of patients. The monocyte and DC NF-{kappa}B response to LPS is thus a novel phenotypic and likely pathogenetic marker for human T1DM. SHP-1 is at least one NF-{kappa}B regulatory mechanism which might be induced as a result of abnormal inflammatory signaling responses in T1DM monocytes.
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article
Collections: 2009 Higher Education Research Data Collection
UQ Diamantina Institute Publications
 
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Created: Wed, 25 Mar 2009, 14:50:01 EST by Kylie Hengst on behalf of UQ Diamantina Institute