Synthesis and secretion of tumour necrosis factor-alpha by human monocytic THP-1 cells and chemotaxis induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts.
Human serum albumin minimally-modified by methylglyoxal (MGmin-HSA) stimulated the synthesis and secretion of tumour necrosis factor-alpha (TNF-alpha) from human monocytic THP-1 cells in vitro. Human serum albumin minimally-modified by glucose-derived advanced glycation endproducts (AGEmin-HSA) and human serum albumin highly-modified by glucose-derived advanced glycation endproducts (AGE-HSA) stimulated markedly lower synthesis and secretion of TNF-alpha from THP-1 cells than did MGmin-HSA. The median effective concentration EC50 value of MGmin-HSA for the secretion of TNF-alpha was 5.8 +/- 0.3 microM and the maximal secretion was 0.28 +/- 0.01 ng TNF-alpha/ml (n = 12) for incubations containing 5 x 10(5) cells/ml. MGmin-HSA (0.2-2.0 microM) also stimulated chemotaxis of THP-1 cells in vitro but AGE-HSA did not in this concentration range. The EC50 value of MGmin-HSA for the chemotactic response was 0.44 +/- 0.07 microM (n = 15). Similar induction of the synthesis and secretion of TNF-alpha and chemotaxis by monocytes in response to MGmin-HSA in vivo may contribute to atherosclerosis in macro- and micro-angiopathy, particularly in the development of chronic clinical complications of diabetes mellitus.
Abordo
E A
EA
Department of Biological and Chemical Sciences, University of Essex, Colchester, UK.
Thornalley
P J
PJ
D001120:Arginine; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D003553:Cystine; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008239:Lysine; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000737:chemistry / Q000494:pharmacology*; D012709:Serum Albumin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D003553:Cystine; D011765:Pyruvaldehyde; D001120:Arginine; D008239:Lysine