title: Differential regulation of astrocyte prostaglandin response by kinins: possible role for mitogen activated protein kinases.
abstract: The role of kinins, well known as peripheral inflammatory mediators, in the modulation of brain inflammation is not completely understood. The present data show that bradykinin, a B2 receptor agonist, enhanced both basal and lipopolysaccharide (LPS)-induced cyclooxygenase-2 mRNA and protein levels and prostaglandin E2 synthesis in primary rat astrocytes. By contrast, Lys-des-Arg(9)-bradykinin, which is a bradykinin breakdown product and a selective kinin B1 receptor agonist, attenuated both basal and LPS-induced astrocyte cyclooxygenase-2 mRNA levels and prostaglandin E2 production. Pre-treating the cells with p42/p44 MAPK but not with JNK or p38 inhibitors completely abrogated PGE2 synthesis in cells stimulated with LPS in the presence of bradykinin or bradykinin B1 receptor agonist. Bradykinin, but not the bradykinin B1 receptor agonist, augmented p42/p44 MAPK phosphorylation. The phosphorylation of JNK and p38 was not altered upon exposure to Bradykinin or the bradykinin B1 receptor agonist. These results suggest that the dual delayed effect of kinins on PGE2 synthesis may be due to differential regulation of COX-2 and signaling molecules such as p42/p44 MAPKs. Thus, kinins may exert opposing actions on brain inflammation and neurodegenerative diseases.
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
authors.forename: Nofar
authors.initials: N
authors.lastname: Torika
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
authors.forename: Talia
authors.initials: T
authors.lastname: Filipovich-Rimon
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Asraf
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Roasso
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Danon
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel. Electronic address: fleisher@bgu.ac.il.
authors.forename: Sigal
authors.initials: S
authors.lastname: Fleisher-Berkovich
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000502:physiology*; D007705:Kinins / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007705:Kinins; D011453:Prostaglandins; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone
keywords: Bradykinin; Bradykinin B(1) receptor agonist; Lipopolysaccaride; Primary astrocytes