Leukotriene B4, administered via intracerebroventricular injection, attenuates the antigen-induced asthmatic response in sensitized guinea pigs.

Leukotriene B4, administered via intracerebroventricular injection, attenuates the antigen-induced asthmatic response in sensitized guinea pigs.
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通过脑室内注射白三烯 B4 可以减轻致敏豚鼠抗原诱导的哮喘反应。

DOI:
10.1186/1742-2094-7-12
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发表时间:
2010-02-11
影响因子:
9.3
通讯作者:
Xie QM
Xie QM
中科院分区:
医学1区
文献类型:
--
作者:
Zhu YL;Zhang SJ;Deng YM;Dong XW;Jiang JX;Xie QM

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尽管集中在哮喘炎症的病理生理学的深入研究,很少有人知道如何在哮喘发作期间神经内分泌和免疫系统之间的串扰调节炎症反应。最近,我们发现抗原激发哮喘大鼠脑和肺组织中细胞因子和白三烯B4(LTB 4)的相应变化。在这里,我们研究了LTB 4如何与神经内分泌免疫系统相互作用,调节致敏豚鼠抗原诱导的哮喘反应。卵清蛋白致敏豚鼠通过吸入抗原进行攻击。通过脑室内注射(i. c. v.)攻毒前30分钟。使用抗原激发前后的Penh值评价气道收缩反应。在激发后24 h评价肺组织中的炎症反应。采用反相高效液相色谱法(RP-HPLC)检测肺和脑匀浆中LTB 4的含量。用酶联免疫吸附法测定血浆促肾上腺皮质激素(ACTH)和皮质酮(CORT)水平。抗原攻击损害肺功能和增加肺组织中的炎性细胞浸润。这些反应可被LTB 4,30 ng i. c. v.,卵清蛋白致敏的豚鼠。抗原攻击豚鼠的肺和脑匀浆中LTB 4含量显著增加。此外,LTB 4通过i. c. v.给药显著增加抗原攻击前血浆中的CORT和ACTH水平,并且抗原攻击后血浆中的CORT和ACTH水平进一步增加。U75302,100 ng i.c.v.,完全阻断LTB 4的作用。此外,U 75302,100 ng通过i. c. v.注射,显着降低肺匀浆中的LTB 4含量,但在脑匀浆中没有。哮喘发作期间脑中LTB 4水平增加通过BLT 1受体下调气道收缩反应和炎症。LTB 4刺激下丘脑-垂体-肾上腺轴可能导致全身糖皮质激素增加,反过来,这将反馈抑制哮喘反应。
Despite intensive studies focused on the pathophysiology of asthmatic inflammation, little is known about how cross-talk between neuroendocrine and immune systems regulates the inflammatory response during an asthmatic attack. We recently showed corresponding changes of cytokines and leukotriene B4 (LTB4) in brain and lung tissues of antigen-challenged asthmatic rats. Here, we investigated how LTB4 interacts with the neuroendocrine-immune system in regulating antigen-induced asthmatic responses in sensitized guinea pigs. Ovalbumin-sensitized guinea pigs were challenged by inhalation of antigen. Vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor) was given via intracerebroventricular injection (i.c.v.) 30 min before challenge. Airway contraction response was evaluated using Penh values before and after antigen challenge. The inflammatory response in lung tissue was evaluated 24 h after challenge. The LTB4 content of lung and brain homogenate preparations was detected by reversed phase high-performance liquid chromatography (RP-HPLC). Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using ELISA kits. Antigen challenge impaired pulmonary function and increased inflammatory cell infiltration in lung tissue. These responses could be significantly suppressed by LTB4, 30 ng i.c.v., in ovalbumin-sensitized guinea pigs. LTB4 content of lung and brain homogenates from antigen-challenged guinea pigs was significantly increased. In addition, administration of LTB4 via i.c.v. markedly increased CORT and ACTH level in plasma before antigen challenge, and there were further increases in CORT and ACTH levels in plasma after antigen challenge. U75302, 100 ng i.c.v., completely blocked the effects of LTB4. In addition, U75302, 100 ng via i.c.v. injection, markedly decreased LTB4 content in lung homogenates, but not in brain homogenates. Increased LTB4 levels in brain during asthmatic attacks down-regulates airway contraction response and inflammation through the BLT1 receptor. Stimulation of the hypothalamic-pituitary-adrenal axis by LTB4 may result in an increase in systemic glucocorticoids which, in turn, would feed back to suppress the asthmatic response.
DOI: 10.1111/j.1749-6632.2008.03975.x
发表时间: 2009-01-01
期刊: NEUROIMMUNOMODULATION: FROM FUNDAMENTAL BIOLOGY TO THERAPY
影响因子: --
作者:
Berczi, Istvan;Quintanar-Stephano, Andres;Kovacs, Kalman
通讯作者: Kovacs, Kalman
DOI: 10.1111/j.1471-4159.2007.04830.x
发表时间: 2007-11-01
影响因子: 4.7
作者:
Farias, Santiago E.;Zarini, Simona;Heidenreich, Kim A.
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DOI: 10.4049/jimmunol.174.8.4979
发表时间: 2005-04-15
影响因子: 4.4
作者:
Miyahara, N;Takeda, K;Gelfand, EW
通讯作者: Gelfand, EW
DOI: 10.1016/s1056-8719(98)00021-5
发表时间: 1998-04-01
影响因子: 1.9
作者:
Chong, BTY;Agrawal, DK;Townley, RG
通讯作者: Townley, RG
DOI: 10.1016/j.neurobiolaging.2006.06.007
发表时间: 2007-09-01
影响因子: 4.2
作者:
Chinnici, Cinzia M.;Yao, Yuemang;Pratico, Domenico
通讯作者: Pratico, Domenico