Induction of synthesis and secretion of interleukin Ip 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 (MG(min)-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 mu M ligand, IL-1 beta synthesis was (pg/10(6) cells): MG(min)-HSA 484.5 +/- 50.3; AGE-HSA 30.6 +/- 2.0 (n = 3). IL-1 beta synthesis increased markedly with MG(min)-HSA concentrations > 5 mu M. 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.