Anti-inflammatory effects of short chain fatty acids in IFN-γ-stimulated RAW 264.7 murine macrophage cells:: Involvement of NF-κB and ERK signaling pathways
Anti-inflammatory effects of short chain fatty acids in IFN-γ-stimulated RAW 264.7 murine macrophage cells:: Involvement of NF-κB and ERK signaling pathways
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DOI：
10.1016/j.intimp.2006.08.015
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发表时间：
2007-01-01
影响因子：
5.6
通讯作者：
Kim, Hee-Sun
中科院分区：
文献类型：
--
作者：
Park, Jin-Sun;Lee, Eun-Jung;Kim, Hee-Sun
巨噬细胞的过度活化导致异常细胞死亡和慢性炎性疾病。因此，调节巨噬细胞介导的细胞毒性有望成为治疗各种炎症性疾病的新策略。在这项研究中，发现三种类型的短链脂肪酸（丁酸钠（NaB）、苯丁酸钠（NaPB）、苯乙酸钠（NaPA））在IFN-γ刺激的RAW 264.7细胞中具有抗炎作用。它们抑制由IFN-γ诱导的iNOS、TNF-α和IL-6的表达，同时增强抗炎细胞因子IL-10的表达。它们的抗炎活性顺序为NaB > NaPB > NaPA。进一步的机制研究表明，这三种药物抑制NF-κ B的DNA结合和转录活性，NF-κ B是炎症的重要调节剂。此外，这些药物抑制IFN-γ诱导的ERK 1/2磷酸化，而不影响Jak/STAT活性。对NF-κ B和ERK的抑制作用也为NaB > NaPB > NaPA。结果表明，NF-κ B和ERK信号通路至少部分参与了这些SCFA的抗炎活性。考虑到SCFAs通常存在于体内并且具有很少的副作用，它们可能是用于预防和/或治疗各种炎性疾病的有希望的药剂。(c)2006 Elsevier B. V.保留所有权利。
The overactivation of macrophages causes abnormal cell death and chronic inflammatory diseases. Therefore, the modulation of macrophage-mediated cytotoxicity is expected to become a new therapeutic strategy for various inflammatory diseases. In this study, three types of short chain fatty acids (sodium butyrate (NaB), sodium phenylbutyrate (NaPB), sodium phenylacetate (NaPA)) were found to have anti-inflammatory effects in IFN-gamma-stimulated RAW 264.7 cells. They inhibited the expression of iNOS, TNF-alpha, and IL-6 induced by IFN-gamma, while they enhanced the expression of the anti-inflammatory cytokine, IL-10. Their potency as anti-inflammatory agents was in the order of NaB > NaPB > NaPA. Further mechanistic studies revealed these three agents to repress the DNA binding and transcriptional activities of NF-kappa B, which is an important modulator of inflammation. In addition, these agents repressed the IFN-gamma-induced ERK1/2 phosphorylation without affecting the Jak/STAT activities. The potency of NF-kappa B and ERK inhibition was also in the order of NaB > NaPB > NaPA. The results suggest that the NF-kappa B and ERK signaling pathways are at least in part involved in the anti-inflammatory activities of these SCFAs. Considering that SCFAs are normally present in the body and have few side effects, they might be promising agents for the prevention and/or treatment of various inflammatory diseases. (c) 2006 Elsevier B.V. All rights reserved.