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Modulation of inflammatory response in mice with severe autoimmune disease by thymic peptide thymulin and an inhibitor of NF-kappaB signalling

机译:胸腺肽胸腺肽和NF-κB信号转导抑制剂对重度自身免疫性疾病小鼠炎症反应的调节

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To investigate some cellular and molecular aspects of the autoimmune response and anti-inflammatory efficiency of potential therapeutic agents in a severe form of experimental autoimmune encephalomyelitis (sEAE), an inhibitor of NF-kappaB signalling, IKK Inhibitor XII, and/or thymic peptide thymulin, were injected intraperitoneally at 1.8 and 0.15 mg/kg e.o.d, respectively, to C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein and several adjuvants. The immunization induced high lethality in three weeks. The biphasic cytokine response observed in earlier and delayed phases was attributed to the activity of Th1 and Th17 cells, respectively. Phosphorylation of RelA protein from the NF-kappaB family increased during the earlier phase and decreased in the delayed phase. SAPMNK signalling protein and heat shock protein Hsp72 Significantly increased in lymphocytes. Both the IKK Inhibitor XII and thymulin reduced disease severity, attenuated immune imbalance, and increased mouse life-span. Co-administration of the agents produced no additive effect. Both the inhibitor and thymulin reduced the Th1 response but not the Th17 response. Therefore, RelA-associated Thl activation and RelA-independent Th17 activation occurred in sEAE. Thymulin and the inhibitor demonstrate similar patterns of activity, potentially through the RelA pathway inhibition, resulting in a partial therapeutic effect on the animals' health status. (C) 2015 Elsevier B.V. All rights reserved.
机译:在严重形式的实验性自身免疫性脑脊髓炎(sEAE),NF-κB信号传导抑制剂,IKK抑制剂XII和/或胸腺肽胸腺肽中,研究潜在治疗剂的自身免疫应答和抗炎功效的细胞和分子方面分别以1.8和0.15 mg / kg eod腹膜内注射分别用髓鞘少突胶质细胞糖蛋白和几种佐剂免疫的C57BL / 6小鼠。免疫在三周内诱发了高致死性。在早期和延迟阶段观察到的双相细胞因子反应分别归因于Th1和Th17细胞的活性。来自NF-κB家族的RelA蛋白的磷酸化在早期阶段增加而在延迟阶段减少。 SAPMNK信号蛋白和热休克蛋白Hsp72在淋巴细胞中显着增加。 IKK抑制剂XII和百里香素均可降低疾病的严重程度,减轻免疫失衡,并延长小鼠的寿命。药剂的共同给药没有产生加和作用。抑制剂和胸腺素都降低了Th1反应,但没有降低Th17反应。因此,在sEAE中发生了RelA相关的Th1激活和独立于RelA的Th17激活。 Thymulin和抑制剂表现出相似的活性模式,可能通过RelA途径抑制,从而对动物的健康状况产生部分治疗作用。 (C)2015 Elsevier B.V.保留所有权利。

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