【摘 要】
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白细胞介素8(IL-8),又名CXC趋化因子8(CXCL8),在炎症和正常生理条件下能趋化特异性和非特异性的免疫细胞到达特定部位并激活免疫细胞,调控免疫反应。硬骨鱼中,IL-8对外周血淋
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白细胞介素8(IL-8),又名CXC趋化因子8(CXCL8),在炎症和正常生理条件下能趋化特异性和非特异性的免疫细胞到达特定部位并激活免疫细胞,调控免疫反应。硬骨鱼中,IL-8对外周血淋巴细胞、头肾淋巴细胞和中性粒细胞等的趋化功能已经被验证,但是IL-8发挥免疫调节功能的机制仍不清楚。因此,本文通过研究草鱼IL-8介导的胞内信号通路以及IL-8与其它炎症因子的相互作用等初步探讨硬骨鱼IL-8免疫调节机制。首先,通过优化重组表达和纯化条件获得了高纯度的重组草鱼IL-8蛋白(rgcIL-8),然后用rgcIL-8处理草鱼头肾白细胞(HKL)发现,草鱼IL-8能够通过MAPK和NF?B信号通路诱导自身以及IL-1?和TNF-?等促炎因子基因的表达;草鱼IL-8抗体中和实验发现内源性IL-8部分参与IL-1?对其自身的调控,而草鱼IL-1?抗体中和实验则发现内源性IL-1?不参与IL-8对其自身和IL-1?基因的调控;同时,草鱼IL-8能够诱导HKLs中诱导型一氧化氮合成酶(iNOS)基因的表达和一氧化氮(NO)的产生。本研究证明草鱼IL-8通过MAPK和NF?B等信号通路调节促炎因子基因的表达,揭示了草鱼IL-8发挥免疫调节功能的胞内信号转导途径。IL-8和IL-1?相互作用的研究,为深入探讨草鱼IL-8的免疫调节功能奠定了基础。草鱼IL-8能够诱导NO的产生,填补了IL-8对NO的调节方面的空白。综上所述,本文的研究不仅完善了草鱼IL-8免疫功能,也为草鱼养殖病害的免疫防治提供了潜在的靶点。
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