Alcohol abuse and smoking alter inflammatory mediator production by pulmonary and systemic immune cells
Alcohol abuse and smoking alter inflammatory mediator production by pulmonary and systemic immune cells
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DOI：
10.1152/ajplung.00242.2015
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发表时间：
2016-03-15
影响因子：
4.9
通讯作者：
Burnham, Ellen L.
中科院分区：
文献类型：
--
作者：
Gaydos, Jeanette;McNally, Alicia;Burnham, Ellen L.
酒精使用障碍 (AUD) 和吸烟与社区获得性肺炎和急性呼吸窘迫综合征的易感性增加有关。机制尚未完全确定，但可能包括免疫细胞（包括肺泡巨噬细胞（AM）和外周血单核细胞（PBMC））对病原体反应的改变。我们试图确定 AUD 和吸烟与人类受试者在脂多糖 (LPS) 或脂磷壁酸 (LTA) 刺激后 AM 和 PBMC 表达 IFN γ、IL-1 β、IL-6 和 TNF α 的关系。来自具有 AUD 和对照组的健康受试者的 AM 和 PBMC，与吸烟相匹配，在存在和不存在抗氧化剂前体 N-乙酰半胱氨酸 (10 mM) 的情况下与 LPS (1 μg/ml) 或 LTA (5 μg/ml) 一起培养。测量细胞培养物上清液中的细胞因子。 AM 和 PBMC 中 IFN γ、IL-1 β、IL-6 和 TNF α 的表达响应 LPS 和 LTA 的刺激而显着增加。 AUD 与 AM 和 PBMC 响应 LPS 产生的促炎细胞因子（特别是 IFN γ 和 IL-1 β）的增加有关。吸烟降低了 AUD 对 AM 细胞因子表达的影响。基础AM和PBMC Toll样受体-2和-4的表达与细胞因子表达的差异没有明显的相关性；然而，添加 N-乙酰半胱氨酸与 LPS 或 LTA 会导致 AM 和 PBMC 细胞因子分泌减少，特别是在当前吸烟者中。我们的研究结果表明，AM 和 PBMC 免疫细胞对 LPS 和 LTA 的反应受到 AUD 和吸烟的影响，其机制可能包括细胞氧化应激的改变。
Alcohol use disorders (AUDs) and tobacco smoking are associated with an increased predisposition for community-acquired pneumonia and the acute respiratory distress syndrome. Mechanisms are incompletely established but may include alterations in response to pathogens by immune cells, including alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs). We sought to determine the relationship of AUDs and smoking to expression of IFN gamma, IL-1 beta, IL-6, and TNF alpha by AMs and PBMCs from human subjects after stimulation with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). AMs and PBMCs from healthy subjects with AUDs and controls, matched on smoking, were cultured with LPS (1 mu g/ml) or LTA (5 mu g/ml) in the presence and absence of the antioxidant precursor N-acetylcysteine (10 mM). Cytokines were measured in cell culture supernatants. Expression of IFN gamma, IL-1 beta, IL-6, and TNF alpha in AMs and PBMCs was significantly increased in response to stimulation with LPS and LTA. AUDs were associated with augmented production of proinflammatory cytokines, particularly IFN gamma and IL-1 beta, by AMs and PBMCs in response to LPS. Smoking diminished the impact of AUDs on AM cytokine expression. Expression of basal AM and PBMC Toll-like receptors-2 and -4 was not clearly related to differences in cytokine expression; however, addition of N-acetylcysteine with LPS or LTA led to diminished AM and PBMC cytokine secretion, especially among current smokers. Our findings suggest that AM and PBMC immune cell responses to LPS and LTA are influenced by AUDs and smoking through mechanisms that may include alterations in cellular oxidative stress.