title: Potent anti-inflammatory activity of pyrenocine A isolated from the marine-derived fungus Penicillium paxilli Ma(G)K.
abstract: Very little is known about the immunomodulatory potential of secondary metabolites isolated from marine microorganisms. In the present study, we characterized pyrenocine A, which is produced by the marine-derived fungus Penicillium paxilli Ma(G)K and possesses anti-inflammatory activity. Pyrenocine A was able to suppress, both pretreatment and posttreatment, the LPS-induced activation of macrophages via the inhibition of nitrite production and the synthesis of inflammatory cytokines and PGE2. Pyrenocine A also exhibited anti-inflammatory effects on the expression of receptors directly related to cell migration (Mac-1) as well as costimulatory molecules involved in lymphocyte activation (B7.1). Nitrite production was inhibited by pyrenocine A in macrophages stimulated with CpG but not Poly I:C, suggesting that pyrenocine A acts through the MyD88-dependent intracellular signaling pathway. Moreover, pyrenocine A is also able to inhibit the expression of genes related to NF κ B-mediated signal transduction on macrophages stimulated by LPS. Our results indicate that pyrenocine A has promissory anti-inflammatory properties and additional experiments are necessary to confirm this finding in vivo model.
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Júlio de Mesquita Filho", 14801-902 Araraquara, SP, Brazil.
authors.forename: Thaís Regina
authors.initials: TR
authors.lastname: Toledo
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Júlio de Mesquita Filho", 14801-902 Araraquara, SP, Brazil ; Faculdade de Medicina Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Naiara N
authors.initials: NN
authors.lastname: Dejani
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Júlio de Mesquita Filho", 14801-902 Araraquara, SP, Brazil.
authors.forename: Luis Gustavo Silva
authors.initials: LG
authors.lastname: Monnazzi
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, 13560-970 São Carlos, SP, Brazil.
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Kossuga
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, 13560-970 São Carlos, SP, Brazil.
authors.forename: Roberto G S
authors.initials: RG
authors.lastname: Berlinck
authors.affiliation: Departamento de Bioquímica e Microbiologia, Instituto de Biociências, Universidade Estadual Paulista "Júlio de Mesquita Filho", 13506-900 Rio Claro, SP, Brazil.
authors.forename: Lara D
authors.initials: LD
authors.lastname: Sette
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Júlio de Mesquita Filho", 14801-902 Araraquara, SP, Brazil.
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007166:Immunosuppressive Agents / Q000737:chemistry; D007249:Inflammation; D008070:Lipopolysaccharides / Q000737:chemistry*; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry; D010407:Penicillium / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009573:Nitrites; D011753:Pyrones; C052579:pyrenocine A; D015232:Dinoprostone