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互叶白千层浓缩物(MAC)的免疫调节活性:抑制脂多糖诱导的髓系细胞系中NF-κB激活和细胞因子产生

Immunomodulatory activity of Melaleuca alternifolia concentrate (MAC): inhibition of LPS-induced NF-κB activation and cytokine production in myeloid cell lines.

作者信息

Low Pauline, Clark Amanda M, Chou Tz-Chong, Chang Tsu-Chung, Reynolds Maxwell, Ralph Stephen J

机构信息

School of Medical Sciences and Griffith Health Research Institute, Griffith University, Gold Coast campus, Southport, Queensland 4222, Australia.

National Defense Medical Center, Taipei, Taiwan.

出版信息

Int Immunopharmacol. 2015 May;26(1):257-64. doi: 10.1016/j.intimp.2015.03.034. Epub 2015 Apr 6.

DOI:10.1016/j.intimp.2015.03.034
PMID:25858876
Abstract

Melaleuca alternifolia concentrate (MAC) is a mixture predominantly composed of monoterpenoids and sesquiterpenes, refined from the essential oil of the tea tree by removing up to 99% of the more toxic, hydrophobic monoterpenes. MAC was examined here for its immunomodulatory effects on the human THP1 and murine RAW264.7 myeloid leukemic cell lines as models for macrophage-like cells. Firstly, MAC levels were determined that did not affect either the survival or proliferation of these cell lines in vitro. Next, the levels of lipopolysaccharide (LPS)-induced production of cytokines (IL-6, TNFα, IL-10, GM-CSF, IFNγ and IL-3) were examined from the myeloid cell lines using multiplex assays. Many of the LPS-inducible cytokines produced by either cell lines could be significantly inhibited by MAC. Closer examination of the mechanism of action of MAC showed that it inhibited the LPS-induced activation of IκB phosphorylation and nuclear factor (NF)-κB signalling and translocation, inhibiting iNOS protein expression and NO production. These results demonstrate that MAC exerts its immunomodulatory effects by inhibiting NF-κB signalling activation and levels of cytokine production by macrophage-like cell lines.

摘要

互叶白千层浓缩物(MAC)是一种主要由单萜类化合物和倍半萜组成的混合物,通过去除高达99%毒性更强的疏水性单萜类化合物,从茶树精油中提炼而来。本文以人THP1和小鼠RAW264.7髓系白血病细胞系作为巨噬细胞样细胞模型,研究了MAC对其的免疫调节作用。首先,测定了MAC在体外不影响这些细胞系存活或增殖的浓度水平。接下来,使用多重分析法检测了髓系细胞系中脂多糖(LPS)诱导的细胞因子(IL-6、TNFα、IL-10、GM-CSF、IFNγ和IL-3)产生水平。MAC能够显著抑制两种细胞系产生的多种LPS诱导型细胞因子。对MAC作用机制的进一步研究表明,它抑制了LPS诱导的IκB磷酸化激活以及核因子(NF)-κB信号传导和易位,抑制了诱导型一氧化氮合酶(iNOS)蛋白表达和一氧化氮(NO)产生。这些结果表明,MAC通过抑制NF-κB信号激活和巨噬细胞样细胞系的细胞因子产生水平发挥其免疫调节作用。

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