Acute induction of inflammatory cytokine expression after γ-irradiation in the rat:: Effect of an NF-κb inhibitor

Acute induction of inflammatory cytokine expression after γ-irradiation in the rat:: Effect of an NF-κb inhibitor
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DOI:
10.1016/j.ijrobp.2003.09.039
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发表时间:
2004-02-01
影响因子:
7
通讯作者:
Mathé, D
Mathé, D
中科院分区:
医学1区
文献类型:
--
作者:
Linard, C;Marquette, C;Mathé, D

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目的:肠肌层内的病理变化可能是导致急性辐射诱导的炎症的细胞因子的起源。我们特别感兴趣的核转录因子κ B(NF-κ B)的激活,参与调节细胞因子expression.Methods和材料:细胞因子的表达进行了分析,在回肠肌层逆转录-聚合酶链反应(RT-PCR)在3小时,6小时,3天后,10-戈伊γ全身照射大鼠。结果:照射后3 h和6 h,白细胞介素(IL)-1 β、肿瘤坏死因子α(TNF-α)和IL-6 mRNA表达增加,IL-6和IL-8表达在照射后3d升高。另一方面,抗炎细胞因子IL-10的水平在第3天显著降低。第3天IL-6的过表达与IL-6受体(gp 130/gp 80)和细胞因子信号传导抑制因子-3(SOCS 3)基因的上调相结合。CAPE治疗并没有显着改变IL-1 β或TNF-α的表达在照射大鼠;它增加了IL-10的表达在6小时,但在第3天没有影响。CAPE治疗抑制辐射诱导的IL-6,IL-6受体(IL-6 rs),和SOCS 3的表达在3 day.Conclusion:在体内,辐射诱导了一系列的炎症反应,涉及转录因子NF-κ B;这种炎症减少CAPE治疗。(C)2004年爱思唯尔公司
Purpose: The pathologic changes within the intestinal muscle layer may be at the origin of the cytokines that account for acute radiation-induced inflammation. We were specifically interested in evaluating the efficacy of an inhibitor of nuclear transcription factor kappa B (NF-kappaB) activation that is involved in regulating cytokine expression.Methods and Materials: Cytokine expression was analyzed in the ileal muscularis layer by reverse transcriptase-polymerase chain reaction (RT-PCR) at 3 h, 6 h, and 3 days after a 10-Gy gamma whole-body irradiation of rats. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally (30 mg/kg) 15 min before irradiation and once a day for 3 days.Results: Interleukin (IL)-1beta, tumor necrosis factor alpha (TNF- alpha), and IL-6 mRNA increased at 3 h and 6 h after irradiation, and expression of IL-6 and IL-8 was elevated at 3 days. On the other hand, levels of the anti-inflammatory cytokine IL-10 were markedly lower on Day 3. Overexpression of IL-6 on Day 3 was combined with upregulation of the IL-6 receptors (gp130/gp80) and suppressor of cytokine signaling-3 (SOCS3) genes. CAPE treatment did not significantly change IL-1beta or TNF-alpha expressions in the irradiated rats; it increased IL-10 expression at 6 h but had no effect on it on Day 3. CAPE treatment inhibited the radiation-induced expression of IL-6, IL-6 receptors (IL-6rs), and SOCS3 at 3 days.Conclusion: In vivo, irradiation induced a cascade of inflammatory responses that involved the transcription factor NF-kappaB; this inflammation was reduced by CAPE treatment. (C) 2004 Elsevier Inc.