Induction of synthesis and secretion of interleukin 1 beta in the human monocytic THP-1 cells by human serum albumins modified with methylglyoxal and advanced glycation endproducts.
Human serum albumin modified with 1-2 methylglyoxal residues per molecule of protein (MGmin-HSA) stimulated the synthesis and secretion of interleukin 1 beta (IL-1 beta) from human monocytic THP-1 cells in vitro. It was a more potent inducer of IL-1 beta synthesis than human serum albumin highly-modified with glucose-derived advanced glycation endproducts (AGE-HSA). With 20 microM ligand. IL-1 beta synthesis was (pg/10(6) cells): MGmin-HSA 484.5 +/- 50.3; AGE-HSA 30.6 +/- 2.0 (n = 3). IL-1 beta synthesis increased markedly with MGmin-HSA concentrations > 5 microM. IL-1 beta synthesis and secretion from monocytes in response to methylglyoxal-modified proteins in vivo may contribute to the development of macro- and micro-angiopathy, particularly in diabetes mellitus.
Westwood
M E
ME
Department of Chemistry and Biological Chemistry, University of Essex, Colchester, UK.
Thornalley
P J
PJ
D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism*; D007938:Leukemia; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000494:pharmacology*; D012709:Serum Albumin / Q000187:drug effects* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017127:Glycation End Products, Advanced; D007375:Interleukin-1; D012709:Serum Albumin; D011765:Pyruvaldehyde