Acute alcohol intoxication suppresses the pulmonary ELR-negative CXC chemokine response to lipopolysaccharide
Acute alcohol intoxication suppresses the pulmonary ELR-negative CXC chemokine response to lipopolysaccharide
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DOI：
10.1016/j.alcohol.2007.06.002
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发表时间：
2007-08-01
期刊：
影响因子：
2.3
通讯作者：
Shellito, Judd E.
中科院分区：
文献类型：
--
作者：
Happel, Kyle I.;Rudner, Xiaowen;Shellito, Judd E.
酗酒会损害肺部对感染的免疫反应，并增加细菌性肺炎的发病率和死亡率。脂多糖 (LPS) 攻击后，急性酒精中毒会抑制带有 Glu-Leu-Arg 基序 (ELR+) 的 CXC 趋化因子的肺部表达，但其对吸引 T 细胞的结构相关的 ELR-CXC 趋化因子的影响尚不清楚。因此，我们研究了急性酒精中毒对气管内 (i.t) LPS 对由 γ（MIG 或 CXCL9）诱导的 ELR-CXC 趋化因子单因子、干扰素诱导蛋白 10（IP-10 或 CXCL10）和干扰素诱导 T 细胞 α 趋化剂（I-TAC 或 CXCL11）诱导的肺部反应的影响。雄性C5713L/6或C3H/HeN小鼠在给药前30分钟腹腔注射乙醇(3.0g/kg)或磷酸盐缓冲盐水。 LPS 挑战。在 0、2、6 和 16 小时测量趋化因子 mRNA 转录本。急性酒精中毒抑制了肺部响应脂多糖的所有三种趋化因子基因的表达。在同一时间过程中，肺 IFN-γ mRNA 也受到急性中毒的抑制。在 MH-S 肺泡巨噬细胞系中进一步研究了乙醇对趋化因子分泌的体外影响。外源干扰素 (IFN)-γ 增强了 IP-10、MIG 和 I-TAC 对 LPS 的反应，而这些反应因暴露于乙醇而减弱。尽管 Erk 1/2 磷酸化存在剂量依赖性抑制，但酒精暴露不会影响攻击期间 MH-S 细胞核因子 kappa beta p65 的核定位。此外，在急性乙醇存在下，磷酸信号转导和转录激活因子 I 并未减少，从而表明急性中毒不会影响 MH-S 细胞中的 IFN-γ 信号传导。 LPS 攻击后 4 天，急性乙醇中毒中度损害了 CD3+ T 细胞向肺泡腔的募集。这些结果表明急性乙醇中毒是肺部炎症期间淋巴细胞趋化剂表达的重要抑制剂。 (C) 2007 Elsevier Inc. 保留所有权利。
Alcohol abuse impairs the pulmonary immune response to infection and increases the morbidity and mortality of bacterial pneumonia. Acute alcohol intoxication suppresses lung expression of CXC chemokines bearing the Glu-Leu-Arg motif (ELR+) following lipopolysaccharide (LPS) challenge, but its effect on the structurally related ELR- CXC chemokines, which attract T cells, is unknown. We therefore investigated the effect of acute alcohol intoxication on the pulmonary response to intratracheal (i.t.) LPS challenge for the ELR- CXC chemokines monokine induced by gamma (MIG or CXCL9), interferon-inducible protein 10 (IP-10 or CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC or CXCL11). Male C5713L/6 or C3H/HeN mice were given an intraperitoneal injection of ethanol (3.0 g/kg) or phosphate buffered saline 30 min before i.t. LPS challenge. Chemokine mRNA transcripts were measured at 0, 2, 6, and 16 h. Acute alcohol intoxication inhibited the lung's expression of all three chemokine genes in response to LPS. Lung IFN-gamma mRNA was also inhibited by acute intoxication over the same time course. The in vitro effect of ethanol on chemokine secretion was further studied in the MH-S alveolar macrophage cell line. IP-10, MIG, and I-TAC in response to LPS were enhanced by exogenous interferon (IFN)-gamma, and these responses were blunted by exposure to ethanol. Alcohol exposure did not affect MH-S cell nuclear factor kappa beta p65 nuclear localization during challenge, despite dose-dependent inhibition of Erk 1/2 phosphorylation. In addition, phospho-signal transduction and activator of transcription I was not decreased in the presence of acute ethanol, thereby indicating that acute intoxication does not affect IFN-gamma signaling in MH-S cells. Recruitment of CD3+ T cells into the alveolar space 4 days after LPS challenge was moderately impaired by acute ethanol intoxication. These results implicate acute ethanol intoxication as a significant inhibitor of lymphocyte chemoattractant expression during pulmonary inflammation. (C) 2007 Elsevier Inc. All rights reserved.