Augmented responses to ozone in obese carboxypeptidase E-deficient mice
Augmented responses to ozone in obese carboxypeptidase E-deficient mice
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DOI：
10.1152/ajpregu.00306.2005
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发表时间：
2006-01-01
影响因子：
2.8
通讯作者：
Shore, SA
中科院分区：
文献类型：
--
作者：
Johnston, RA;Theman, TA;Shore, SA
肥胖羧肽酶E缺陷小鼠对臭氧的增强反应。Am J Physiol Regul Integr Comp Physiol 290：R126-R133,2006.2005年7月7日首次出版；DOI：10.1152/ajpregu。00306.2005。-我们之前曾报道，与野生型(C57BL/6)对照组相比，瘦素缺乏(ob/ob)导致的肥胖小鼠臭氧(O-3)诱导的气道高反应性(AHR)和炎症反应增强。为了确定这种对O-3增加的反应是否独立于肥胖的形式，我们研究了O-3诱导的AHR和CPE(FAT)小鼠的炎症。这些小鼠肥胖是由于编码羧基肽酶E(CPE)的基因突变造成的，CPE是一种在处理前激素和与饱腹感和能量消耗有关的前神经肽方面非常重要的酶。通过强迫振荡测量，暴露于空气后，Cpefat与野生型小鼠相比，对静脉注射乙酰甲胆碱的呼吸道反应性增加。此外，与空气暴露相比，CPE(脂肪)小鼠在O-3暴露(2ppm，3h)后24 h的气道反应性增加，但在野生型小鼠中没有增加。与空气暴露对照组相比，O-3暴露组大鼠肺泡灌洗液(BALF)蛋白、IL-6、KC、MIP-2、MCP-1、可溶性肿瘤坏死因子受体(sTNFR1和sTNFR2)及BALF中性粒细胞数均增加。除sTNFR1和sTNFR2外，所有这些结果指标在Cpefat小鼠与野生型小鼠相比都更高。血清sTNFR1、sTNFR2、MCP-1、瘦素和血白细胞与野生型小鼠相比升高，即使在没有O-3暴露的情况下也是如此，类似于在人类肥胖中观察到的慢性全身炎症。这些结果表明，无论肥胖的形式如何，O-3诱导的AHR增加和炎症是肥胖小鼠的一致特征。这些结果还表明，慢性全身炎症可能会增强肥胖小鼠对O-3的呼吸道反应。
Augmented responses to ozone in obese carboxypeptidase E-deficient mice. Am J Physiol Regul Integr Comp Physiol 290: R126 - R133, 2006. First published July 7, 2005; doi: 10.1152/ajpregu. 00306.2005. - We reported previously that mice obese as a result of leptin deficiency (ob/ob) have enhanced ozone (O-3)- induced airway hyperresponsiveness (AHR) and inflammation compared with wild-type (C57BL/6) controls. To determine whether this increased response to O-3 was independent of the modality of obesity, we examined O-3-induced AHR and inflammation in Cpe(fat) mice. These mice are obese as a consequence of a mutation in the gene encoding carboxypeptidase E (Cpe), an enzyme important in processing prohormones and proneuropeptides involved in satiety and energy expenditure. Airway responsiveness to intravenous methacholine, measured by forced oscillation, was increased in Cpefat vs. wild-type mice after air exposure. In addition, compared with air exposure, airway responsiveness was increased 24 h after O-3 exposure (2 ppm for 3 h) in Cpe(fat) but not in wild-type mice. Compared with air-exposed controls, O-3 exposure increased bronchoalveolar lavage fluid (BALF) protein, IL-6, KC, MIP-2, MCP-1, and soluble TNF receptors (sTNFR1 and sTNFR2) as well as BALF neutrophils. With the exception of sTNFR1 and sTNFR2, all of these outcome indicators were greater in Cpefat vs. wild-type mice. Serum sTNFR1, sTNFR2, MCP-1, leptin, and blood leukocytes were elevated in Cpefat compared with wild-type mice even in the absence of O-3 exposure, similar to the chronic systemic inflammation observed in human obesity. These results indicate that increased O-3-induced AHR and inflammation are consistent features of obese mice, regardless of the modality of obesity. These results also suggest that chronic systemic inflammation may enhance airway responses to O-3 in obese mice.