title: The role of PKC/ERK1/2 signaling in the anti-inflammatory effect of tetracyclic triterpene euphol on TPA-induced skin inflammation in mice.
abstract: Inflammation underlies the development and progression of a number of skin disorders including psoriasis, atopic dermatitis and cancer. Therefore, novel antiinflammatory agents are of great clinical interest for prevention and treatment of these conditions. Herein, we demonstrated the underlying molecular mechanisms of the antiinflammatory activity of euphol, a tetracyclic triterpene isolated from the sap of Euphorbia tirucalli, in skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice. Topical application of euphol (100 μg/ear) significantly inhibited TPA-induced ear edema and leukocyte influx through the reduction of keratinocyte-derived chemokine (CXCL1/KC) and macrophage inflammatory protein (MIP)-2 levels. At the intracellular level, euphol reduced TPA-induced extracellular signal-regulated protein kinase (ERK) activation and cyclooxygenase-2 (COX-2) upregulation. These effects were associated with euphol's ability to prevent TPA-induced protein kinase C (PKC) activation, namely PKCα and PKCδ isozymes. Our data indicate that topical application of euphol markedly inhibits the inflammatory response induced by TPA. Thus, euphol represents a promising agent for the management of skin diseases with an inflammatory component.
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, Santa Catarina, Brazil.
authors.forename: Giselle F
authors.initials: GF
authors.lastname: Passos
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Medeiros
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Marcon
authors.forename: Andrey F Z
authors.initials: AF
authors.lastname: Nascimento
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Pianowski
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007810:Lanosterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D012871:Skin Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007810:Lanosterol; C062557:euphol; D051546:Cyclooxygenase 2; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013755:Tetradecanoylphorbol Acetate