Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Júlio de Mesquita Filho", 14801-902 Araraquara, SP, Brazil.
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.
Mediators Inflamm. 2014;2014:767061. doi: 10.1155/2014/767061. Epub 2014 Jan 19.
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.
关于从海洋微生物中分离得到的次生代谢产物的免疫调节潜力，人们知之甚少。在本研究中，我们对来源于海洋真菌青霉（Penicillium paxilli Ma(G)K）的具有抗炎活性的化合物pyrenocine A 进行了研究。Pyrenocine A 能够通过抑制亚硝酸盐的产生以及炎症细胞因子和 PGE2 的合成，对 LPS 诱导的巨噬细胞激活进行预处理和后处理抑制。Pyrenocine A 还对与细胞迁移直接相关的受体（Mac-1）以及参与淋巴细胞激活的共刺激分子（B7.1）的表达表现出抗炎作用。Pyrenocine A 能够抑制 CpG 而非 Poly I:C 刺激的巨噬细胞中产生的亚硝酸盐，这表明 Pyrenocine A 通过 MyD88 依赖性细胞内信号通路发挥作用。此外，Pyrenocine A 还能够抑制 LPS 刺激的巨噬细胞中与 NF-κB 介导的信号转导相关的基因表达。我们的研究结果表明，Pyrenocine A 具有有前景的抗炎特性，需要进一步的体内实验来证实这一发现。
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