Synthesis and secretion of tumour necrosis factor- α by human monocytic THP-1 cells and chemotaxis induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts

Abstract

Human serum albumin minimally-modified by methylglyoxal (MG min-HSA) stimulated the synthesis and secretion of tumour necrosis factor- α (TNF- α) from human monocytic THP-1 cells in vitro. Human serum albumin minimally-modified by glucose-derived advanced glycation endproducts (AGE min-HSA) and human serum albumin highly-modified by glucose-derived advanced glycation endproducts (AGE-HSA) stimulated markedly lower synthesis and secretion of TNF- α from THP-1 cells than did MG min-HSA. The median effective concentration EC 50 value of MG min-HSA for the secretion of TNF- α was 5.8±0.3 μM and the maximal secretion was 0.28±0.01 ng TNF- α/ml ( n=12) for incubations containing 5×10 5 cells/ml. MG min-HSA (0.2–2.0 μM) also stimulated chemotaxis of THP-1 cells in vitro but AGE-HSA did not in this concentration range. The EC 50 value of MG min-HSA for the chemotactic response was 0.44±0.07 μM ( n=15). Similar induction of the synthesis and secretion of TNF- α and chemotaxis by monocytes in response to MG min-HSA in vivo may contribute to atherosclerosis in macro- and micro-angiopathy, particularly in the development of chronic clinical complications of diabetes mellitus.