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巨噬细胞集落刺激因子(CSF-1)可诱导金鱼(Carassius auratus L.)巨噬细胞的促炎基因表达并增强其抗菌反应。

Macrophage colony-stimulating factor (CSF-1) induces pro-inflammatory gene expression and enhances antimicrobial responses of goldfish (Carassius auratus L.) macrophages.

作者信息

Grayfer Leon, Hanington Patrick C, Belosevic Miodrag

机构信息

Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6E2E9, Canada.

出版信息

Fish Shellfish Immunol. 2009 Mar;26(3):406-13. doi: 10.1016/j.fsi.2008.12.001. Epub 2008 Dec 10.

Abstract

We report on the regulation of pro-inflammatory functions of goldfish macrophages and induction of gene expression by recombinant goldfish CSF-1 (rgCSF-1). Recombinant goldfish TNFalpha-2 (rg TNFalpha-2), rgIFNgamma but not rgTGFbeta induced time-dependent increase of CSF-1 expression in macrophages. Treatment of goldfish macrophages with rgCSF-1 increased expression of several immune genes including CXCL-8 (=IL-8), CCL-1, TNFalpha-1, TNFalpha-2, IL-1beta-1, IL-1beta-2, IL-12-p35, IL-12-p40, IFN, IL-10 and iNOS A and B. The rgCSF-1 treatment did not significantly alter the mRNA levels of TGFbeta and NRAMP in macrophages up to 48h post treatment. However, at 72h post treatment, the expression of TGFbeta increased whereas that of NRAMP decreased. The treatment of macrophages with rgCSF-1 enhanced their respiratory burst and nitric oxide responses that were abrogated after addition of soluble CSF-1 receptor (sCSF-1R) to cell cultures. Macrophages exhibited a concentration-dependent chemotactic response toward rgCSF-1 as well as an increase in phagocytic activity that was abrogated after addition of sCSF-1R to cell cultures. Our results indicate that in addition to being an important growth factor of goldfish macrophages, rgCSF-1 also plays a central role in the regulation of their pro-inflammatory responses.

摘要

我们报告了金鱼巨噬细胞促炎功能的调节以及重组金鱼集落刺激因子-1(rgCSF-1)对基因表达的诱导作用。重组金鱼肿瘤坏死因子α-2(rg TNFα-2)、rg干扰素γ(rgIFNγ)而非rg转化生长因子β(rgTGFβ)可诱导巨噬细胞中CSF-1表达随时间增加。用rgCSF-1处理金鱼巨噬细胞可增加多种免疫基因的表达,包括CXCL-8(=白细胞介素-8)、CCL-1、肿瘤坏死因子α-1、肿瘤坏死因子α-2、白细胞介素-1β-1、白细胞介素-1β-2、白细胞介素-12-p35、白细胞介素-12-p40、干扰素、白细胞介素-10以及诱导型一氧化氮合酶A和B。rgCSF-1处理在处理后48小时内未显著改变巨噬细胞中TGFβ和天然抗性相关巨噬蛋白(NRAMP)的mRNA水平。然而,在处理后72小时,TGFβ的表达增加,而NRAMP的表达降低。用rgCSF-1处理巨噬细胞可增强其呼吸爆发和一氧化氮反应,在细胞培养物中添加可溶性CSF-受体(sCSF-1R)后这些反应被消除。巨噬细胞对rgCSF-1表现出浓度依赖性趋化反应以及吞噬活性增加,在细胞培养物中添加sCSF-1R后这种增加被消除。我们的结果表明,rgCSF-1除了是金鱼巨噬细胞的重要生长因子外,在调节其促炎反应中也起着核心作用。

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