Cigarette smoke-mediated inflammatory and oxidative responses are strain-dependent in mice
Cigarette smoke-mediated inflammatory and oxidative responses are strain-dependent in mice
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DOI：
10.1152/ajplung.00439.2007
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发表时间：
2008-06-01
影响因子：
4.9
通讯作者：
Rahman, Irfan
中科院分区：
文献类型：
--
作者：
Yao, Hongwei;Edirisinghe, Indika;Rahman, Irfan
各种小鼠模型已被用于研究肺气肿/慢性阻塞性肺病的发病机制。香烟烟雾（CS）的影响被认为是品系依赖性的，因为某些小鼠品系对肺气肿的发展更敏感或更有抵抗力。然而，小鼠品系对CS作用的易感性的分子基础尚不清楚。我们研究了CS对大多数常用小鼠品系肺的影响，以研究CS效应易感性的分子机制。将C57 BL/6 J、A/J、AKR/J、CD-1和129 SvJ小鼠连续暴露于CS 3天，并在这些小鼠的肺中评估炎症和氧化反应的各种参数。我们发现，C57 BL/6 J菌株是高度敏感的，A/J，AKR/J和CD-1菌株是中度敏感的，和129 SvJ菌株是抵抗肺部炎症和氧化反应的CS暴露。与耐药小鼠品系相比，对CS作用更敏感的小鼠品系表现出增加的肺部炎症细胞流入，NF-κ B和p38 MAPK的活化，以及基质金属蛋白酶-9和NF-κ B依赖性促炎细胞因子水平的增加。同样，谷胱甘肽水平的降低与敏感小鼠品系与耐药品系相比脂质过氧化产物水平的增加有关。因此，我们根据炎症和氧化反应的模式鉴定了易感和耐药小鼠品系。敏感和耐药小鼠品系的鉴定可能有助于研究CS对炎症影响的分子机制和CS暴露小鼠模型的药理学干预研究。
A variety of mouse models have been used to study the pathogenesis of pulmonary emphysema/chronic obstructive pulmonary disease. The effect of cigarette smoke (CS) is believed to be strain dependent, because certain mouse strains are more susceptible or resistant to development of emphysema. However, the molecular basis of susceptibility of mouse strains to effects of CS is not known. We investigated the effect of CS on lungs of most of the commonly used mouse strains to study the molecular mechanism of susceptibility to effects of CS. C57BL/6J, A/J, AKR/J, CD-1, and 129SvJ mice were exposed to CS for 3 consecutive days, and various parameters of inflammatory and oxidative responses were assessed in lungs of these mice. We found that the C57BL/6J strain was highly susceptible, the A/J, AKR/J, and CD-1 strains were moderately susceptible, and the 129SvJ strain was resistant to lung inflammatory and oxidant responses to CS exposure. The mouse strain that was more susceptible to effects of CS showed augmented lung inflammatory cell influx, activation of NF-kappa B and p38 MAPK, and increased levels of matrix metalloproteinase-9 and NF-kappa B-dependent proinflammatory cytokines compared with resistant mouse strains. Similarly, decreased levels of glutathione were associated with increased levels of lipid peroxidation products in susceptible mouse strains compared with resistant strains. Hence, we identified the susceptible and resistant mouse strains on the basis of the pattern of inflammatory and oxidant responses. Identification of sensitive and resistant mouse strains could be useful for studying the molecular mechanisms of effects of CS on inflammation and pharmacological interventional studies in CS-exposure mouse models.