PMID- 24358331 OWN - NLM STAT- MEDLINE DCOM- 20140916 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 12 DP - 2013 TI - A pseudopterane diterpene isolated from the octocoral Pseudopterogorgia acerosa inhibits the inflammatory response mediated by TLR-ligands and TNF-alpha in macrophages. PG - e84107 LID - 10.1371/journal.pone.0084107 [doi] LID - e84107 AB - 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-alpha) and TLRs- induced response in macrophages. Compound 1 inhibited the expression and secretion of the inflammatory mediators TNF-alpha, interleukin (IL)-6, IL-1beta, 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 IkappaBalpha degradation and subsequent activation of NFkappaB. 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-alpha 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. FAU - Gonzalez, Yisett AU - Gonzalez Y AD - Centro de Biologia Celular y Molecular de Enfermedades, Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Ciudad de Panama, Panama ; Department of Biotechnology, Acharya Nagarjuna University, Guntur, India. FAU - Doens, Deborah AU - Doens D AD - Centro de Biologia Celular y Molecular de Enfermedades, Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Ciudad de Panama, Panama ; Department of Biotechnology, Acharya Nagarjuna University, Guntur, India. FAU - Santamaria, Ricardo AU - Santamaria R AD - Centro de Descubrimiento de Drogas y Biodiversidad, Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Ciudad de Panama, Panama FAU - Ramos, Marla AU - Ramos M AD - Centro de Biologia Celular y Molecular de Enfermedades, Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Ciudad de Panama, Panama FAU - Restrepo, Carlos M AU - Restrepo CM AD - Centro de Biologia Celular y Molecular de Enfermedades, Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Ciudad de Panama, Panama ; Department of Biotechnology, Acharya Nagarjuna University, Guntur, India. FAU - Barros de Arruda, Luciana AU - Barros de Arruda L AD - Laboratorio de Genetica e Imunologia das Infeccoes Virais, Departamento de Virologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil. FAU - Lleonart, Ricardo AU - Lleonart R AD - Centro de Biologia Celular y Molecular de Enfermedades, Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Ciudad de Panama, Panama FAU - Gutierrez, Marcelino AU - Gutierrez M AD - Centro de Descubrimiento de Drogas y Biodiversidad, Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Ciudad de Panama, Panama FAU - Fernandez, Patricia L AU - Fernandez PL AD - Centro de Biologia Celular y Molecular de Enfermedades, Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Ciudad de Panama, Panama LA - eng GR - U01 TW006634/TW/FIC NIH HHS/United States GR - TW006634/TW/FIC NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131216 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Anti-Inflammatory Agents) RN - 0 (B7-1 Antigen) RN - 0 (B7-2 Antigen) RN - 0 (Diterpenes) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (Ligands) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Toll-Like Receptors) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Anthozoa/*chemistry MH - Anti-Inflammatory Agents/chemistry/*pharmacology MH - B7-1 Antigen/metabolism MH - B7-2 Antigen/metabolism MH - Cells, Cultured MH - Diterpenes/chemistry/*pharmacology MH - Enzyme Activation MH - Female MH - Inflammation Mediators/metabolism MH - Interleukin-6/genetics/metabolism MH - Ligands MH - Lipopolysaccharides/immunology MH - Macrophage Activation/drug effects MH - Macrophages/*drug effects/immunology/*metabolism MH - Macrophages, Peritoneal/drug effects/immunology/metabolism MH - Male MH - Mice MH - Mitogen-Activated Protein Kinases/metabolism MH - NF-kappa B/metabolism MH - Toll-Like Receptors/*metabolism MH - Tumor Necrosis Factor-alpha/genetics/*metabolism PMC - PMC3865250 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/12/21 06:00 MHDA- 2014/09/17 06:00 PMCR- 2013/12/16 CRDT- 2013/12/21 06:00 PHST- 2013/06/06 00:00 [received] PHST- 2013/11/12 00:00 [accepted] PHST- 2013/12/21 06:00 [entrez] PHST- 2013/12/21 06:00 [pubmed] PHST- 2014/09/17 06:00 [medline] PHST- 2013/12/16 00:00 [pmc-release] AID - PONE-D-13-23643 [pii] AID - 10.1371/journal.pone.0084107 [doi] PST - epublish SO - PLoS One. 2013 Dec 16;8(12):e84107. doi: 10.1371/journal.pone.0084107. eCollection 2013.