title: Bradykinin promotes Toll like receptor-4 expression in human gingival fibroblasts.
abstract: Bacterial infections are a potent mechanism for enzymatic generation of kinins such as bradykinin (BK), a universal mediator for inducing inflammatory reaction by associating with the B2 receptor and stimulating liberation of arachidonic acid and synthesis of prostaglandin E2 (PGE2). In this study we evaluate the role of bradykinin in regulating the expression of TLR4 receptor in human gingival fibroblasts. We examine the ability of bradykinin to modulate inflammatory response of human gingival fibroblasts to Gram-negative components and evaluated the role of Toll-like receptors (TLR)-4 in the co-operation between bradykinin and bacterial pathogens. We show that treatment with bradykinin promotes TLR4 receptor expression in human gingival fibroblasts (HGF) and amplifies inflammatory responses to the bacterial components of Gram-negative bacteria. The TLR4 expression induced by bradykinin was blocked with Hoe 140, a B2R antagonist. When HGF cells were incubated with BK resulted of an increased in cyclooxygenase-2 (COX-2) expression and prostaglandin E2 synthesis. Bradykinin and lipopolysaccharide, a specific TLR4 ligand stimulated COX-2 expression. In other series of experiments we found that ERK, phosphatidylinositol-3 kinase, protein kinase C and NFkB are involved in BK promoted-increased in TLR4 expression. The results demonstrate that bradykinin up-regulates the expression of TLR4 and promotes an additive increase in inflammatory responses to lipopolysaccharides.
authors.affiliation: Laboratorio de Bioquímica, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, Ciudad de México, Mexico. gloriafoodntounam@gmail.com
authors.forename: Gloria
authors.initials: G
authors.lastname: Gutiérrez-Venegas
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Arreguín-Cano
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández-Bermúdez
mesh_terms: D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D043782:Receptor, Bradykinin B2; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C065679:icatibant; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D001920:Bradykinin