title: Proline-rich polypeptide complex (PRP) regulates secretion of inflammatory mediators by its effect on NF-kappaB activity.
abstract: A proline-rich polypeptide complex (PRP) with immunoregulatory and procognitive activities shows beneficial effects in the Alzheimer's disease (AD). The mechanism of action of PRP is not yet fully clarified, we have shown that the PRP complex inhibits overproduction of reactive oxygen species, nitric oxide and proinflammatory cytokines induced by lipopolysaccharide (LPS). LPS stimulation exerts its inflammatory effects through the activation of the classical nuclear factor-kappaB (NF-kappaB) pathway. The results presented in this study showed the ability of PRP to inhibit the NF-kappaB activity induced by LPS while it increased activity of NF-kappaB in untreated cells. Examining the effect of PRP on IkappaB it was shown that relative level of IkappaB was lowered in the presence of PRP. It seems that in cells untreated with LPS, PRP can activate proteasome system and stimulate IkappaB degradation. Our results suggest that the regulatory effect of PRP on inflammatory processes may be associated with the influence of PRP on NF-kappaB translocation. Inhibitory effect of PRP on NF-kappaB activity might, at least in part, contribute to the beneficial therapeutic effects in the case of Alzheimer's disease.
authors.affiliation: Department of Immunochemistry, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla, 53-114 Wrocław, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zabłocka
authors.forename: Jakub
authors.initials: J
authors.lastname: Siednienko
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Mitkiewicz
authors.forename: Wojciech A
authors.initials: WA
authors.lastname: Gorczyca
authors.forename: Józef
authors.initials: J
authors.lastname: Lisowski
authors.forename: Maria
authors.initials: M
authors.lastname: Janusz
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D055232:Proline-Rich Protein Domains; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D051550:I-kappa B Kinase