High molecular weight hyaluronic acid inhibits advanced glycation endproduct-induced NF-kappaB activation and cytokine expression.
Advanced glycation endproducts (AGEs), which accumulate on long-lived proteins and protein deposits (amyloids), induce the expression of proinflammatory cytokines through NF-kappaB-dependent pathways. Hyaluronic acid with a molecular weight above 1.2 MDa (HMW-HA) inhibits the AGE-induced activation of the transcription factor NF-kappaB and the NF-kappaB-regulated cytokines interleukin-1alpha, interleukin-6 and tumor necrosis factor-alpha. Since the molecular weight of hyaluronic acid in humans decreases with age and under conditions of oxidative stress, it is likely that the protective effect of HMW-HA against AGE-induced cellular activation is lost at sites of chronic inflammation and in older age.
Physiological Chemistry I, Biocenter, Würzburg, Germany.
A
A
Neumann
R
R
Schinzel
D
D
Palm
P
P
Riederer
G
G
Münch
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008262:Macrophage Activation; D051379:Mice; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D016207:Cytokines; D017127:Glycation End Products, Advanced; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D006820:Hyaluronic Acid