Role of prostaglandin I2 in airway remodeling induced by repeated allergen challenge in mice.
Role of prostaglandin I2 in airway remodeling induced by repeated allergen challenge in mice.
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前列腺素 I2 在小鼠反复过敏原激发诱导的气道重塑中的作用。
DOI：
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发表时间：
2003
影响因子：
6.4
通讯作者：
H. Nagai
中科院分区：
文献类型：
--
作者：
K. Nagao;Hiroyuki Tanaka;M. Komai;T. Masuda;S. Narumiya;H. Nagai
最近，我们证明前列腺素(PG)I2通过受体IP在过敏反应中具有调节作用；然而，PGI2在与慢性气道炎相关的气道重塑中的作用尚未阐明。在本研究中，我们利用IP基因缺陷小鼠研究了PGI2在变应原诱导的气道重塑中的作用。用含明胶的卵白蛋白(OVA)致敏小鼠，雾化吸入OVA，每天3wk。最后一次抗原吸入24小时后，进行支气管肺泡灌洗、生化和组织病理学检查。在野生型小鼠中，致敏动物长期接触变应原可导致炎症白细胞(包括嗜酸性粒细胞和淋巴细胞)数量、辅助性T细胞(Th2)细胞因子(IL-4、IL-5和IL-13)水平、血清中OVA特异性免疫球蛋白(Ig)E和IgG1水平以及右肺羟脯氨酸含量增加，这与支气管肺泡灌洗液中转化生长因子-β1水平有关。此外，反复过敏原激发后，杯状细胞增生和上皮下纤维化也被发现。相反，IP基因的破坏显著增加了所有这些参数。这些结果表明，PGI2在过敏原诱导的气道重塑、气道嗜酸性炎症、Th2细胞因子的产生和IgE的产生中具有调节作用，PGI2激动剂是治疗过敏性哮喘的一种治疗方法。
Recently, we demonstrated that prostaglandin (PG)I2 has a regulatory role in allergic responses through the receptor, IP; however, the role of PGI2 in airway remodeling associated with chronic airway inflammation has not been elucidated. In the present study, we examined the role of PGI2 in allergen-induced airway remodeling using IP gene-deficient mice. Mice were sensitized to ovalbumin (OVA) with alum, and exposed daily for 3 wk to aerosolized OVA. Twenty-four hours after the final antigen inhalation, bronchoalveolar lavage, biochemical, and histopathologic examinations were performed. In wild-type mice, prolonged allergen exposure in sensitized animals induced the increases in the numbers of inflammatory leukocytes (including eosinophils and lymphocytes), levels of T helper type 2 (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13), levels of OVA-specific immunoglobulin (Ig)E and IgG1 in serum, and amount of hydroxyproline in the right lungs associated with transforming growth factor-beta1 levels in bronchoalveolar lavage fluid. Moreover, goblet cell hyperplasia and subepithelial fibrosis were also appreciated after repeated allergen challenge. In contrast, the disruption of IP gene significantly augmented all these parameters. These findings suggest that PGI2 has a regulatory role in allergen-induced airway remodeling as well as airway eosinophilic inflammation, Th2 cytokine production and IgE production, and that a PGI2 agonist is a therapeutic approach for the treatment of airway remodeling in allergic asthma.
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DOI：
10.1165/ajrcmb.17.3.2733
发表时间：
1997-09-01
影响因子：
6.4
作者：
Minshall, EM;Leung, DYM;Hamid, Q
通讯作者：
Hamid, Q
DOI：
10.1164/ajrccm.151.1.7812551
发表时间：
1995-01-01
影响因子：
24.7
作者：
PADRID, P;SNOOK, S;LEFF, AR
通讯作者：
LEFF, AR
影响因子：
15.9
作者：
Longphre, M;Li, D;Basbaum, C
通讯作者：
Basbaum, C
影响因子：
15.9
作者：
Tilley, SL;Coffman, TM;Koller, BH
通讯作者：
Koller, BH
影响因子：
15.9
作者：
Smith, WL;Langenbach, R
通讯作者：
Langenbach, R