Scottish Fish Immunology Research Centre, Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, AB24 2TZ Scotland, UK.
Fish Shellfish Immunol. 2011 Jan;30(1):215-23. doi: 10.1016/j.fsi.2010.10.010. Epub 2010 Oct 20.
Glucocorticoid actions on the immune system are diverse and cell type dependent, and little is known about cell type-specific interactions and cross-talk between hormones and cytokines. In this study we have analyzed the gene expression patterns of the rainbow trout macrophage cell line RTS-11 by quantitative PCR, after exposure to combinations of cortisol plus a pro-inflammatory cytokine (e.g. recombinant trout IL-1β, IFN-γ), type I IFN or a PAMP (LPS or poly I:C). Several key genes of the inflammatory process were targetted to assess whether any modulation of their expression occurred due to the addition of cortisol to this cell line. Incubation of macrophages for 3 or 6 h with a physiological concentration of cortisol caused a decrease in expression of IL-6 and IL-8, but no significant changes were observed for the other genes examined. Co-stimulation of cortisol with the inflammatory agents resulted in a general suppression of genes related to the inflammatory response. Cortisol inhibited the up-regulation of IL-8 by all the stimulants after 3 h of co-incubation. Suppression of the up-regulation of IL-6 by rIL-1β, rIFN-γ and poly I:C, of γIP by rIFN-γ or poly I:C, and of Cox-2 by rIL-1β was seen after 6 h. In contrast, cortisol in combination with the pro-inflammatory agents has a synergistic effect on IL-10 expression, an anti-inflammatory molecule, suggesting that the activation of certain macrophage functions that lead to the resolution of inflammation occurs in fish macrophages in response to cortisol treatment.
糖皮质激素对免疫系统的作用具有多样性和细胞类型依赖性,而对于激素和细胞因子之间的细胞类型特异性相互作用和串扰知之甚少。在这项研究中,我们通过定量 PCR 分析了虹鳟巨噬细胞系 RTS-11 的基因表达模式,这些细胞系在暴露于皮质醇加促炎细胞因子(例如重组虹鳟白细胞介素 1β、干扰素-γ)、I 型干扰素或 PAMP(LPS 或 poly I:C)的组合后。选择了几个炎症过程的关键基因来评估由于向该细胞系中添加皮质醇而导致其表达是否发生任何变化。用生理浓度的皮质醇孵育巨噬细胞 3 或 6 小时会导致 IL-6 和 IL-8 的表达减少,但未观察到其他检查基因的显着变化。皮质醇与炎症剂共同刺激导致与炎症反应相关的基因普遍受到抑制。皮质醇在共孵育 3 小时后抑制了所有刺激物对 IL-8 的上调。rIL-1β、rIFN-γ 和 poly I:C 对 IL-6 的上调抑制、γIP 对 rIFN-γ 或 poly I:C 的上调抑制以及 Cox-2 对 rIL-1β 的上调抑制在 6 小时后出现。相比之下,皮质醇与促炎剂联合使用对抗炎分子 IL-10 的表达具有协同作用,这表明在鱼类巨噬细胞中,对皮质醇治疗的反应会激活某些导致炎症消退的巨噬细胞功能。