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不同辐射剂量对诱导性T辅助细胞分化及相关细胞因子分泌的影响。

Effects of various radiation doses on induced T-helper cell differentiation and related cytokine secretion.

作者信息

Gao Hui, Dong Zhuo, Gong Xinkou, Dong Juancong, Zhang Yuyu, Wei Wei, Wang Rui, Jin Shunzi

机构信息

Ministry of Health Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China.

The First Hospital of Jilin University, Department of Osteology, Changchun, China.

出版信息

J Radiat Res. 2018 Jul 1;59(4):395-403. doi: 10.1093/jrr/rry011.

Abstract

Exposure to ionizing radiation often induces T helper (Th) cell differentiation, resulting in an imbalance of Th1 and Th2 cellular subtypes, which can affect the efficacy of cancer radiotherapy. The aim of this study was to analyze differential expression of Th1, Th2 and Th3/Type 1 regulatory T cell (Tr1) subtype-related genes and cytokines in mouse thymocytes after high- and low-dose systemic radiation, using functional classification gene arrays and Elisa assays, and to explore the molecular mechanisms underlying radiation's immune effects and their relationship with Th1/Th2 immunity. We found that expression of 8 genes was upregulated after LDR, while expression of 5 genes was downregulated. After HDR, 54 genes were upregulated and 3 genes were downregulated, including genes related to Th1, Th2 and Th3/Tr1 cellular subtypes, Th1/Th2-type immune response genes and transcription factor-related genes. In the foregoing results, LDR and HDR in the thymus induced opposite patterns of expression for Th1-, Th2- and Th3-type related cytokines TGF-β, C/EBP-β and TNF-α. We also found that expression of Interferon-γ (IFN-γ) and Interleukin-2 (IL-2), which have a moderating effect on immune function, was upregulated after LDR. Furthermore, the secretion of negative regulatory factors Interleukin-1β (IL-1β), Interleukin-4 (IL-4), transforming growth factor-β (TGF-β) and Interleukin-21 (IL-21) was reduced after LDR, but HDR produced the opposite effect and stimulated their expression. These findings suggest that LDR may induce a Th1-type immune response, while HDR may lead to a Th2-type immune response.

摘要

暴露于电离辐射通常会诱导辅助性T(Th)细胞分化,导致Th1和Th2细胞亚群失衡,这可能会影响癌症放疗的疗效。本研究的目的是使用功能分类基因芯片和酶联免疫吸附测定(ELISA)分析高剂量和低剂量全身照射后小鼠胸腺细胞中Th1、Th2和Th3/1型调节性T细胞(Tr1)亚群相关基因及细胞因子的差异表达,并探讨辐射免疫效应的分子机制及其与Th1/Th2免疫的关系。我们发现,低剂量辐射后8个基因的表达上调,5个基因的表达下调。高剂量辐射后,54个基因上调,3个基因下调,包括与Th1、Th2和Th3/Tr1细胞亚群相关的基因、Th1/Th2型免疫反应基因和转录因子相关基因。在上述结果中,胸腺中的低剂量辐射和高剂量辐射诱导了Th1、Th2和Th3型相关细胞因子转化生长因子-β(TGF-β)、C/EBP-β和肿瘤坏死因子-α(TNF-α)的相反表达模式。我们还发现,对免疫功能有调节作用的干扰素-γ(IFN-γ)和白细胞介素-2(IL-2)的表达在低剂量辐射后上调。此外,低剂量辐射后负调节因子白细胞介素-1β(IL-1β)、白细胞介素-4(IL-4)、转化生长因子-β(TGF-β)和白细胞介素-21(IL-21)的分泌减少,但高剂量辐射产生相反的效果并刺激它们的表达。这些发现表明,低剂量辐射可能诱导Th1型免疫反应,而高剂量辐射可能导致Th2型免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ae1/6054226/d2d9aff31e8c/rry011f01.jpg

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