Heat shock treatment suppresses angiotensin II-induced activation of NF-κB pathway and heart inflammation:: a role for IKK depletion by heat shock?
Heat shock treatment suppresses angiotensin II-induced activation of NF-κB pathway and heart inflammation:: a role for IKK depletion by heat shock?
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DOI：
10.1152/ajpheart.00102.2004
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发表时间：
2004-09-01
影响因子：
4.8
通讯作者：
Currie, RW
中科院分区：
文献类型：
--
作者：
Chen, Y;Arrigo, AP;Currie, RW
热休克蛋白（Hsps）通过其伴侣活性和与细胞信号通路相互作用来抑制细胞凋亡，从而发挥组织保护作用。在此，我们研究了HS处理对血管紧张素II （ANG II）炎症模型中核因子(NF)-kappaB信号通路的影响。雄性Sprague-Dawley大鼠分为假组和HS-、ANG II-、HS + ANG II-组。HS治疗于ANGⅱ输注开始前24 h进行。HS治疗（42°c, 15 min）使7天ANG II诱导的高血压从191 +/- 4降至147 +/- 3 mmHg （P < 0.01）。心脏组织学染色显示，HS治疗可减少ANGⅱ诱导的白细胞浸润、血管周围和间质炎症以及纤维化。Western blot分析和电泳迁移率转移实验显示，HS处理可抑制心脏nf - κ B核易位和活性。HS处理减少了I κ B激酶α (ikk - α)并使ikk - α磷酸化，抑制了I κ B- α的缺失和磷酸化I κ B- α的积累。HS处理阻断了ANG II诱导的IL-6和ICAM-1在心脏中的表达。ANG II和HS处理诱导高水平表达Hsp27和Hsp70及其磷酸化。Hsp27和Hsp70的磷酸化异构体可能在保护心脏免受ANG II诱导的炎症中发挥重要作用。
Heat shock (HS) proteins ( Hsps) function in tissue protection through their chaperone activity and by interacting with cell signaling pathways to suppress apoptosis. Here, we investigated the effect of HS treatment on the nuclear factor (NF)-kappaB signaling pathway in the angiotensin II (ANG II) model of inflammation. Male Sprague-Dawley rats were divided into sham and HS-, ANG II-, and HS + ANG II- treated groups. HS treatment was administered 24 h before the initiation of ANG II infusion. HS treatment ( 42 degreesC for 15 min) decreased 7-day ANG II- induced hypertension from 191 +/- 4 to 147 +/- 3 mmHg ( P < 0.01). Histological staining of hearts showed that HS treatment reduced ANG II- induced leukocyte infiltration, perivascular and interstitial inflammation, and fibrosis. Heart NF-kappa B nuclear translocation and activity, examined by Western blot analysis and electrophoretic mobility shift assay, was suppressed by HS treatment. HS treatment depleted I kappa B kinase-alpha (IKK-alpha) and phosphorylated IKK-alpha and suppressed the depletion of I kappa B-alpha and the accumulation of phosphorylated I kappa B-alpha. HS treatment blocked ANG II induced expression of IL-6 and ICAM-1 in the heart. ANG II and HS treatment induced high-level expression of Hsp27 and Hsp70 and their phosphorylation. Phosphorylated isoforms of Hsp27 and Hsp70 may play an important role in protecting the heart against ANG II- induced inflammation.