Intracerebroventricular injection of leukotriene B4 attenuates antigen-induced asthmatic response via BLT1 receptor stimulating HPA-axis in sensitized rats.
Intracerebroventricular injection of leukotriene B4 attenuates antigen-induced asthmatic response via BLT1 receptor stimulating HPA-axis in sensitized rats.
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脑室内注射白三烯 B4 可通过 BLT1 受体刺激致敏大鼠的 HPA 轴来减弱抗原诱导的哮喘反应。
DOI：
10.1186/1465-9921-11-39
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发表时间：
2010-04-20
影响因子：
5.8
通讯作者：
Xie QM
中科院分区：
文献类型：
--
作者：
Zhang SJ;Deng YM;Zhu YL;Dong XW;Jiang JX;Xie QM
基础和临床研究表明，下丘脑-垂体-肾上腺（HPA）轴是调节哮喘等慢性炎症性疾病的神经内分泌-免疫通路。我们前期的研究表明，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。在此，我们研究了在致敏大鼠中，脑中升高的LTB 4水平如何与HPA轴相互作用来调节抗原诱导的哮喘反应。卵清蛋白致敏的大鼠通过吸入抗原进行攻击。在激发前30 min通过侧脑室注射（i.c.v）给予大鼠接受溶媒、LTB 4或U 75302（选择性LTB 4 BLT 1受体抑制剂）。在抗原攻击前后测量肺阻力（RL）和动态肺顺应性（Cdyn）。在激发后24小时评估肺组织中的炎症反应。RT-PCR和Western Blot检测下丘脑CRH mRNA和蛋白表达，ELISA检测血浆促肾上腺皮质激素（ACTH）和皮质酮（CORT）水平。抗原激发致敏大鼠肺功能下降，诱发气道炎症，诱发HPA轴反应。通过i.c.v施用LTB 4显著减弱气道收缩和炎症。腹腔注射LTB_4可使致敏大鼠抗原攻击前血浆CORT和ACTH水平显著升高，抗原攻击后血浆CORT和ACTH水平进一步升高。腹腔注射LTB 4后，致敏大鼠下丘脑CRH mRNA和蛋白表达明显增加。BLT 1受体拮抗剂U 75302（10 ng）预处理可完全阻断这些作用，但BLT 2受体拮抗剂LY 255283则不能阻断这些作用。通过i.c.v施用的LTB 4通过其BLT 1受体激活HPA轴来下调气道收缩反应和炎症。这项研究扩展了我们对颅内炎性介质在包括哮喘在内的炎性疾病中的调节作用的概念。LTB 4对HPA轴的有利影响可能有助于解释哮喘发作后的自我缓解现象。
Basic and clinical studies suggest that hypothalamic-pituitary-adrenal (HPA) axis is the neuroendocrine-immnue pathway that functionally regulates the chronic inflammatory disease including asthma. Our previous studies showed corresponding changes of cytokines and leukotriene B4 (LTB4) between brain and lung tissues in antigen-challenged asthmatic rats. Here, we investigated how the increased LTB4 level in brain interacts with HPA axis in regulating antigen-induced asthmatic response in sensitized rats. Ovalbumin-sensitized rats were challenged by inhalation of antigen. Rats received vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor) was given via intracerebroventricular injection (i.c.v) 30 min before challenge. Lung resistance (RL) and dynamic lung compliance (Cdyn) were measured before and after antigen challenge. Inflammatory response in lung tissue was assessed 24 h after challenge. Expression of CRH mRNA and protein in hypothalamus were evaluated by RT-PCR and Western Blot, and plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using the ELISA kits. Antigen challenge decreased pulmonary function and induced airway inflammation, evoked HPA axis response in sensitized rats. Administration of LTB4 via i.c.v markedly attenuated airway contraction and inflammation. Meanwhile, LTB4 via i.c.v markedly increased CORT and ACTH level in plasma before antigen challenge, and followed by further increases in CORT and ACTH levels in plasma after antigen challenge in sensitized rats. Expression of CRH mRNA and protein in hypothalamus were also significantly increased by LTB4 via i.c.v in sensitized rats after antigen challenge. These effect were completely blocked by pre-treatment with BLT1 receptor antagonist U75302 (10 ng), but not by BLT2 antagonist LY255283. LTB4 administered via i.c.v down-regulates the airway contraction response and inflammation through activation of the HPA axis via its BLT1 receptor. This study expands our concept of the regulatory role of intracranial inflammatory mediators in inflammatory diseases including asthma. The favourable effects of LTB4 on the HPA axis may help to explain the phenomenon of self-relief after an asthmatic attack.
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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：
10.1164/rccm.200307-979oc
发表时间：
2004-01-15
影响因子：
24.7
作者：
Forsythe, P;Ebeling, C;Vliagoftis, H
通讯作者：
Vliagoftis, H
影响因子：
3.3
作者：
Joachim, RA;Quarcoo, D;Klapp, BF
通讯作者：
Klapp, BF
影响因子：
15.1
作者：
Kelley, Keith W.;Weigent, Douglas A.;Kooijman, Ron
通讯作者：
Kooijman, Ron
影响因子：
5.9
作者：
Kalogeromitros, Demetrios;Syrigou, E. Katerini I.;Theoharides, Theoharis C.
通讯作者：
Theoharides, Theoharis C.