COX-1, and not COX-2 activity, regulates airway function: relevance to aspirin-sensitive asthma.
COX-1, and not COX-2 activity, regulates airway function: relevance to aspirin-sensitive asthma.
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DOI：
10.1096/fj.08-107979
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Mitchell JA
中科院分区：
文献类型：
--
作者：
Harrington LS;Lucas R;McMaster SK;Moreno L;Scadding G;Warner TD;Mitchell JA
环氧合酶（考克斯）-1和考克斯-2在气道细胞中表达，它们的活性影响诸如气道高反应性的功能。临床数据显示，混合的考克斯-1/考克斯-2抑制剂如阿司匹林，而不是考克斯-2选择性抑制剂如罗非昔布，在敏感个体中诱导支气管收缩和哮喘。这种反常现象尚未得到解释。在这里，我们使用了缺乏功能性考克斯-1（考克斯-1−/−）的转基因小鼠的组织，以及“阿司匹林敏感”患者和对照患者的气道组织来解决这个问题。野生型小鼠的支气管主要含有考克斯-1免疫反应性，并在体外对乙酰胆碱和U46619作出反应而收缩。考克斯-1−/−小鼠的支气管对支气管收缩剂反应过度。考克斯抑制剂（萘普生、双氯芬酸或布洛芬）增加了野生型小鼠组织中的支气管收缩，但对考克斯-1−/−小鼠没有影响。从阿司匹林敏感或对照人类供体培养的细胞含有相似水平的考克斯-1和考克斯-2免疫反应性。阿司匹林敏感或耐受患者细胞中的考克斯活性被选择性阻断考克斯-1的阿司匹林SC 560抑制，但不被选择性抑制考克斯-2的罗非昔布抑制。这些观察结果表明，尽管存在考克斯-2，但考克斯-1在气道中的功能占主导地位，并解释了与阿司匹林敏感性哮喘患者的药物特异性相关的临床观察结果。哈灵顿湖美国，卢卡斯河McMaster，S. K.，莫雷诺湖Scadding，G.，Warner，T. D、米切尔，J. A.考克斯-1而非考克斯-2活性调节气道功能：与阿司匹林敏感性哮喘的相关性
Cyclooxygenase (COX) -1 and COX-2 are expressed in airway cells, where their activities influence functions such as airway hyperreactivity. Clinical data show that mixed COX-1/COX-2 inhibitors such as aspirin, but not COX-2 selective inhibitors such as rofecoxib, induce bronchoconstriction and asthma in sensitive individuals. This anomaly has not yet been explained. Here, we have used tissue from genetically modified mice lacking functional COX-1 (COX-1−/−), as well as airway tissue from “aspirin-sensitive” and control patients to address this issue. Bronchi from wild-type mice contained predominantly COX-1 immunoreactivity and contracted in vitro in response to acetylcholine and U46619. Bronchi from COX-1−/− mice were hyperresponsive to bronchoconstrictors. Inhibitors of COX (naproxen, diclofenac, or ibuprofen) increased bronchoconstriction in tissue from wild-type but not from COX-1−/− mice. Cells cultured from aspirin-sensitive or control human donors contained similar levels of COX-1 and COX-2 immunoreactivity. COX activity in cells from aspirin-sensitive or tolerant patients was inhibited by aspirin, SC560, which blocks COX-1 selectively, but not by rofecoxib, which is a selective inhibitor of COX-2. These observations show that despite the presence of COX-2, COX-1 is functionally predominant in the airways and explains clinical observations relating to drug specificity in patients with aspirin-sensitive asthma.—Harrington, L. S., Lucas, R., McMaster, S. K., Moreno, L., Scadding, G., Warner, T. D., Mitchell, J. A. COX-1, and not COX-2 activity, regulates airway function: relevance to aspirin-sensitive asthma.
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DOI：
10.1073/pnas.89.16.7384
发表时间：
1992-08-15
影响因子：
11.1
作者：
HLA, T;NEILSON, K
通讯作者：
NEILSON, K
影响因子：
4.8
作者：
Mitchell, Jane A.;Lucas, Ruth;Warner, Timothy D.
通讯作者：
Warner, Timothy D.
DOI：
10.1073/pnas.90.24.11693
发表时间：
1993-12-15
影响因子：
11.1
作者：
MITCHELL, JA;AKARASEREENONT, P;VANE, JR
通讯作者：
VANE, JR
影响因子：
8.7
作者：
BishopBailey, D;Pepper, JR;Mitchell, JA
通讯作者：
Mitchell, JA
DOI：
10.1007/bf01972703
发表时间：
1993-01-01
期刊：
AGENTS AND ACTIONS
影响因子：
--
作者：
HULKOWER, KI;COFFEY, JW;MORGAN, DW
通讯作者：
MORGAN, DW