The classical NFkappaB pathway is required for phloroglucinol-induced activation of murine lymphocytes.

The classical NFkappaB pathway is required for phloroglucinol-induced activation of murine lymphocytes.
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DOI:
10.1016/j.bbagen.2010.03.014
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发表时间:
2010-07
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
G. Ahn;Eun-jin Park;H. Park;Y. Jeon;Jehee Lee;J. Park;Y. Jee
G. Ahn;Eun-jin Park;H. Park;Y. Jeon;Jehee Lee;J. Park;Y. Jee
中科院分区:
其他
文献类型:
--
作者:
G. Ahn;Eun-jin Park;H. Park;Y. Jeon;Jehee Lee;J. Park;Y. Jee

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间苯三酚(PG)是一种多酚类化合物,对免疫细胞具有清除自由基、抗肿瘤和免疫调节作用。在本研究中,我们研究了PG的免疫活性及其分子机制,重点研究了核因子-κB (NFκB)的功能激活,这是一个重要的转录因子,参与淋巴细胞的激活、分化和随后的小鼠淋巴细胞募集。方法采用3h -胸腺嘧啶掺入法、Western blot法、细胞内细胞因子法和EMSA法检测PG是否通过NFκB途径参与免疫应答的激活。结果spg通过诱导i - κ b的降解和磷酸化,进而激活nf - κ b p65,从而显著促进淋巴细胞的增殖。此外,PG诱导丝裂原活化蛋白激酶(MAPKs)如ERK1/2、JNK和p38的活化,它们是NFκB通路的上游分子。此外,PG增加了成熟T淋巴细胞中白细胞介素(IL)-2的分泌和IL-2的产生。此外,TPCK通过抑制NFκB的激活,显著降低PG对淋巴细胞的激活。结论PG通过经典的nf - κ b诱导淋巴细胞增殖活性和IL-2分泌,从而诱导淋巴细胞活化。一般意义:本文首次观察了PG对淋巴细胞活化的影响。这些结果也将阐明其潜在机制。
BACKGROUNDPhloroglucinol (PG), a polyphenolic compound, has been proposed to show free radical scavenging, anti-tumor, and immunomodulation effects on immune cells. In this study, we investigated PG for its immunological activity and their molecular mechanisms, specifically focusing on the functional activation of nuclear factor-κB (NFκB), an important transcription factor involved in the activation and differentiation of lymphocytes, and subsequent recruitment of murine lymphocytes.METHODSWe tested whether PG may contribute to the activation of immune response through the NFκB pathway by3H-thymidine incorporation assay, Western blot, intracellular cytokine assays and Electrophoretic mobility shift assay (EMSA) in murine lymphocytes.RESULTSPG markedly enhanced the proliferation of lymphocytes by inducing the degradation and phosphorylation of IκB, which leads to the activation of NFκB p65. Also, PG induced the activation of mitogen-activated protein kinases (MAPKs) such as ERK1/2, JNK, and p38, upstream molecules of NFκB pathway. In addition, PG augmented the secretion of interleukin (IL)-2 in mature T lymphocytes and their production of IL-2. Furthermore, the application of TPCK significantly reduced the activation of lymphocytes by PG via inhibiting the NFκB activation.CONCLUSIONThese results suggest that PG induces the activation of lymphocytes by inducing the proliferative activity and secretion of IL-2 through the classical NFκB.GENERAL SIGNIFICANCEThe effect of PG on lymphocyte activation was assayed for the first time. These results would also elucidate its underlying mechanism.