title: Anti-inflammatory effects of lindenenyl acetate via heme oxygenase-1 and AMPK in human periodontal ligament cells.
abstract: The molecular basis for the anti-inflammatory effects of lindenenyl acetate (LA) was investigated in the lipopolysaccharide (LPS)-stimulated human periodontal ligament (HPDL) cell model. LA concentration-dependently inhibited LPS-induced inducible nitric oxide synthase (iNOS) derived nitric oxide (NO) and cyclooxygenase-2 (COX-2) derived prostaglandin E2 (PGE(2)) production in HPDL cells. LA also attenuated the production of LPS-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12. LA stimulated heme oxygenase-1 (HO-1) protein expression and enzyme activity of HPDL cells in a dose-dependent manner. Pretreatment with the HO-1 inhibitor, tin protoporphyrin (SnPP), attenuated the inhibitory activities of LA on LPS-induced inflammatory NO, PGE(2), IL-1β, TNF-α, IL-6 and IL-12 production. LA induced translocation of Nrf-2. Furthermore, an inhibitor of JNK MAPK abolished LA-induced HO-1 expression. LA exposure up-regulated the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its upstream kinase activators, including LKB1 and Ca2+/calmodulin-dependent protein kinase kinase-II. Furthermore, compound C, a specific AMPK inhibitor, partially blocked the LA-induced anti-inflammatory effect. Taken together, these results indicate that LA has anti-inflammatory activity in HPDL cells that might be mediated by the HO-1, AMPK, JNK MAPK, and Nrf-2 pathways. Thus, LA may serve as a potential therapeutic agent in periodontal disease.
authors.affiliation: College of Pharmacy, Keimyung University, Dae-gu 704-701, Republic of Korea.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Jong-Jin
authors.initials: JJ
authors.lastname: Kim
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010513:Periodontal Ligament / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D012717:Sesquiterpenes; C543034:lindenenyl acetate; D051547:Heme Oxygenase-1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases