title: A pseudopterane diterpene isolated from the octocoral Pseudopterogorgia acerosa inhibits the inflammatory response mediated by TLR-ligands and TNF-alpha in macrophages.
abstract: Several diterpenoids isolated from terrestrial and marine environments have been identified as important anti-inflammatory agents. Although considerable progress has been made in the area of anti-inflammatory treatment, the search for more effective and safer compounds is a very active field of research. In this study we investigated the anti-inflammatory effects of a known pseudopterane diterpene (referred here as compound 1) isolated from the octocoral Pseudopterogorgia acerosa on the tumor necrosis factor- alpha (TNF-α) and TLRs- induced response in macrophages. Compound 1 inhibited the expression and secretion of the inflammatory mediators TNF-α, interleukin (IL)-6, IL-1β, nitric oxide (NO), interferon gamma-induced protein 10 (IP-10), ciclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1) induced by LPS in primary murine macrophages. This effect was associated with the inhibition of IκBα degradation and subsequent activation of NFκB. Compound 1 also inhibited the expression of the co-stimulatory molecules CD80 and CD86, which is a hallmark of macrophage activation and consequent initiation of an adaptive immune response. The anti-inflammatory effect was not exclusive to LPS because compound 1 also inhibited the response of macrophages to TNF-α and TLR2 and TLR3 ligands. Taken together, these results indicate that compound 1 is an anti-inflammatory molecule, which modulates a variety of processes occurring in macrophage activation.
authors.affiliation: Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Ciudad de Panamá, Panamá ; Department of Biotechnology, Acharya Nagarjuna University, Guntur, India.
authors.forename: Yisett
authors.initials: Y
authors.lastname: González
authors.affiliation: Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Ciudad de Panamá, Panamá ; Department of Biotechnology, Acharya Nagarjuna University, Guntur, India.
authors.forename: Deborah
authors.initials: D
authors.lastname: Doens
authors.affiliation: Centro de Descubrimiento de Drogas y Biodiversidad, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Ciudad de Panamá, Panamá
authors.forename: Ricardo
authors.initials: R
authors.lastname: Santamaría
authors.affiliation: Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Ciudad de Panamá, Panamá
authors.forename: Marla
authors.initials: M
authors.lastname: Ramos
authors.affiliation: Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Ciudad de Panamá, Panamá ; Department of Biotechnology, Acharya Nagarjuna University, Guntur, India.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Restrepo
authors.affiliation: Laboratorio de Genética e Imunologia das Infecções Virais, Departamento de Virologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Barros de Arruda
authors.affiliation: Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Ciudad de Panamá, Panamá
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lleonart
authors.affiliation: Centro de Descubrimiento de Drogas y Biodiversidad, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Ciudad de Panamá, Panamá
authors.forename: Marcelino
authors.initials: M
authors.lastname: Gutiérrez
authors.affiliation: Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Ciudad de Panamá, Panamá
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Fernández
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D004224:Diterpenes; D018836:Inflammation Mediators; D015850:Interleukin-6; D008024:Ligands; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases