Open AccessMethylglyoxal modulates immune responses: relevance to diabetes
Author(s) -
Price Claire L.,
Hassi Hafid O. S. Al,
English Nicholas R.,
Blakemore Alexandra I. F.,
Stagg Andrew J.,
Knight Stella C.
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00803.x
Subject(s) - methylglyoxal , glycation , immune system , tumor necrosis factor alpha , chemistry , cytokine , t cell , myeloid , major histocompatibility complex , cytotoxic t cell , biology , immunology , endocrinology , medicine , microbiology and biotechnology , diabetes mellitus , biochemistry , enzyme , in vitro
Increased 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.