%0 Journal Article
%T Potent Anti-Inflammatory Activity of Pyrenocine A Isolated from the Marine-Derived Fungus Penicillium paxilli Ma(G)K
%A Tha赤s Regina Toledo
%A Naiara N. Dejani
%A Luis Gustavo Silva Monnazzi
%A Miriam H. Kossuga
%A Roberto G. S. Berlinck
%A Lara D. Sette
%A Alexandra I. Medeiros
%J Mediators of Inflammation
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/767061
%X 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百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. 1. Introduction Inflammation is a complex host immune system response to stimuli such as microbial infection, endotoxin exposure, burns, and tissue injury. Resident macrophages are the first line of defense against insults and play a key role in the development of inflammation [1, 2]. These phagocytes have a variety of receptors on their surface membrane, termed Pattern Recognition Receptors (PRRs), which facilitate interactions with many molecules present on pathogens, known as PAMPs (pathogen-associated molecular patterns). PRRs such as TLRs (Toll-like receptors) interact with PAMPs that are present on bacteria, viruses, parasites, and fungi, and these interactions play a key role in the activation of phagocytic cells. Lipopolysaccharide (LPS), which is produced by Gram-negative bacteria, binds with a TLR complex composed of CD14/LBP/TLR [1, 2], resulting in the activation of a complex biochemical cascade that promotes the recruitment of MyD88, the activation of protein kinases such as IRAK, recruitment of the adaptor protein TRAF6, and the subsequent activation of NF百B and AP-1 in the nucleus [3]. Cytosolic I百B is only phosphorylated after stimulation by lipopolysaccharide (LPS), resulting in the dissociation of the I百B complex and the translocation of NF百B into the nucleus, permitting interaction with the promoter regions of various genes that encode
%U http://www.hindawi.com/journals/mi/2014/767061/