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AbstractIncreased methylglyoxal (MG) concentrations and formation of advanced glycation end-products (AGEs) are major pathways of glycaemic damage in diabetes, leading to vascular and neuronal complications. Diabetes patients also suffer increased susceptibility to many common infections, the underlying causes of which remain elusive. We hypothesized that immune glycation damage may account for this increased susceptibility. We previously showed that the reaction mixture (RM) for MG glycation of peptide blocks up regulation of CD83 in myeloid cells and inhibits primary stimulation of T cells. Here, we continue to investigate immune glycation damage, assessing surface and intracellular cytokine protein expression by flow cytometry, T-cell proliferation using a carboxyfluorescein succinimidyl ester assay, and mRNA levels by RT-PCR. We show that the immunomodulatory component of this RM was MG itself, with MG alone causing equivalent block of CD83 and loss of primary stimulation. Block of CD83 expression could be reversed by MG scavenger N-acetyl cysteine. Further, MG within RM inhibited stimulated production of interleukin (IL)-10 protein from myeloid cells plus interferon (IFN)-γ and tumour necrosis factor (TNF)-α from T cells. Loss of IL-10 and IFN-γ was confirmed by RT-PCR analysis of mRNA, while TNF-α message was raised. Loss of TNF-α protein was also shown by ELISA of culture supernatants. In addition, MG reduced major histocompatibility complex (MHC) class I expression on the surface of myeloid cells and increased their propensity to apoptose. We conclude that MG is a potent suppressor of myeloid and T-cell immune function and may be a major player in diabetes-associated susceptibility to infection. © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
CitationPrice, C.L., Hassi, H.O.S.A., English, N.R., Blakemore, A.I.F., Stagg, A.J. and Knight, S.C. (2009) Methylglyoxal modulates immune responses: Relevance to diabetes, Journal of Cellular and Molecular Medicine, 14(6B), pp. 1806-1815.
JournalJournal of Cellular and Molecular Medicine
PubMed ID19538479 (pubmed)
Description© 2009 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/j.1582-4934.2009.00803.x
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/
- Methylglyoxal modulates immune responses: relevance to diabetes.
- Authors: Price CL, Hassi HO, English NR, Blakemore AI, Stagg AJ, Knight SC
- Issue date: 2010 Jun
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