title: Arachidonic acid-induced IL-6 expression is mediated by PKC alpha activation in osteoblastic cells.
abstract: There are several pieces of evidence supporting the important role that essential fatty acids (EFAs) and their metabolites play in regulating calcium and bone metabolism, and their relevance to the pathobiology of bone disease, with particular reference to modulating effects on cytokines. We found that arachidonic acid (AA) triggers a cell signal in osteoblasts and leads to the expression of IL-6. To explore the biochemical pathways involved in AA induction of cytokine gene expression, we evaluated the potential protein kinase C (PKC) dependent mechanism accounting for the AA effect on IL-6 gene expression. The osteoblast-like cell line MG-63 was pretreated with calphostin C, a PKC inhibitor, or phorbol 12-myristate 13-acetate (PMA) for an extended period, a condition which causes PKC downregulation, and subsequently with AA. After these treatments, IL-6 gene expression was no longer evident. We also showed that PKC and, in particular, PKC alpha, which are both recruited to the particulate fraction, undergo proteolysis and autophosphorylation; all of these steps are required for PKC activation and, subsequently, for AA-induced signaling. It is interesting that other unsaturated fatty acids, such as oleic acid (OA) or eicosapentaenoic acid (EPA), are unable to induce either PKC activation or IL-6 gene expression.
authors.affiliation: Department of Biological Chemistry, University of Padova, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Bordin
authors.forename: Giovanna
authors.initials: G
authors.lastname: Priante
authors.forename: Estella
authors.initials: E
authors.lastname: Musacchio
authors.forename: Silvia
authors.initials: S
authors.lastname: Giunco
authors.forename: Elena
authors.initials: E
authors.lastname: Tibaldi
authors.forename: Giulio
authors.initials: G
authors.lastname: Clari
authors.forename: Bruno
authors.initials: B
authors.lastname: Baggio
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015118:Eicosapentaenoic Acid; D004789:Enzyme Activation; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D019301:Oleic Acid / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha
chemical_list: D016207:Cytokines; D005231:Fatty Acids, Unsaturated; D015850:Interleukin-6; D016718:Arachidonic Acid; D019301:Oleic Acid; D015118:Eicosapentaenoic Acid; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha