High molecular weight hyaluronic acid inhibits advanced glycation endproduct-induced NF-kappa B activation and cytokine expression

Advanced glycation endproducts (AGEs), which accumulate on long-lived prote ins and protein deposits (amyloids), induce the expression of proinflammato ry cytokines through NF-kappa B-dependent pathways. Hyaluronic acid with a molecular weight above 1.2 MDa (HMW-HA) inhibits the AGE-induced activation of the transcription factor NF-kappa B and the NF-kappa B-regulated cytoki nes interleukin-1 alpha, interleukin-6 and tumor necrosis factor-alpha. Sin ce the molecular weight of hyaluronic acid in humans decreases,vith age and under conditions of oxidative stress, it is likely that the protective eff ect of HMW-HA against AGE-induced cellular activation is lost at sites of c hronic inflammation and in older age. (C) 1999 Federation of European Bioch emical Societies.