Potent Anti-Inflammatory Activity of Pyrenocine A Isolated from the Marine-Derived Fungus Penicillium paxilli Ma(G)K

• Published in: Mediators of Inflammation Vol. 2014; no. 7; pp. 508 - 518
• Main Authors: Medeiros, Alexandra I., Berlinck, Roberto G. S., Kossuga, Miriam H., Monnazzi, Luis Gustavo Silva, Dejani, Naiara N., Toledo, Thaís Regina, Sette, Lara D.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01-01-2014; Hindawi Publishing Corporation; Hindawi Limited
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Cell Adhesion; Cell Line; Cell Membrane - metabolism; CpG Islands; Cytokines - metabolism; Dinoprostone - metabolism; Gene Expression Profiling; Gene Expression Regulation; Immunosuppressive Agents - chemistry; Inflammation; Lipopolysaccharides - chemistry; Lymphocyte Activation; Macrophage Activation; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Mice; Myeloid Differentiation Factor 88 - metabolism; Nitrites - chemistry; Penicillium - chemistry; Pyrones - chemistry; Pyrones - pharmacology; Signal Transduction
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2014/767061

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 NFκB-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.