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
中科院分区:
文献类型:
--
作者:
Linard, C;Marquette, C;Mathé, D
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.