In vivo Angiotensin II AT1 receptor blockade selectively inhibits LPS-induced innate immune response and ACTH release in rat pituitary gland.
In vivo Angiotensin II AT1 receptor blockade selectively inhibits LPS-induced innate immune response and ACTH release in rat pituitary gland.
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DOI：
10.1016/j.bbi.2009.04.012
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发表时间：
2009-10
影响因子：
15.1
通讯作者：
Saavedra, Juan M.
中科院分区：
文献类型：
--
作者：
Sanchez-Lemus, Enrique;Benicky, Julius;Pavel, Jaroslav;Saavedra, Juan M.
关键词：
Systemic lipopolysaccharide (LPS) administration induces an innate immune response and stimulates the hypothalamic-pituitary-adrenal axis. We studied Angiotensin II AT1 receptor participation in the LPS effects with focus on the pituitary gland. LPS (50 μg/kg, i.p.) enhanced, 3 hours after administration, gene expression of pituitary CD14 and that of Angiotensin II AT1A receptors in pituitary and hypothalamic paraventricular nucleus (PVN); stimulated ACTH and corticosterone release; decreased pituitary CRF1 receptor mRNA and increased all plasma and pituitary pro-inflammatory factors studied. The AT1 receptor blocker (ARB) candesartan (1 mg/kg/day, s.c. daily for 3 days before LPS) blocked pituitary and PVN AT1 receptors, inhibited LPS-induced ACTH but not corticosterone secretion and decreased LPS-induced release of TNF-α, IL-1β and IL-6 to the circulation. The ARB reduced LPS-induced pituitary gene expression of IL-6, LIF, iNOS, COX-2 and IκB-α; and prevented LPS-induced increase of nNOS/eNOS activity. The ARB did not affect LPS-induced TNF-α and IL-1β gene expression, IL-6 or IL-1βprotein content or LPS-induced decrease of CRF1 receptors. When administered alone, the ARB increased basal plasma corticosterone levels and basal PGE2 mRNA in pituitary. Our results demonstrate that the pituitary gland is a target for systemically administered LPS. AT1 receptor activity is necessary for the complete pituitary response to LPS and is limited to specific pro-inflammatory pathways. There is a complementary and complex influence of the PVN and circulating cytokines on the initial pituitary response to LPS. Our findings support the proposal that ARBs may be considered for the treatment of inflammatory conditions.
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DOI：
10.1073/pnas.86.2.725
发表时间：
1989-01-01
影响因子：
11.1
作者：
CASTREN, E;SAAVEDRA, JM
通讯作者：
SAAVEDRA, JM
影响因子：
64.8
作者：
BERNHAGEN, J;CALANDRA, T;BUCALA, R
通讯作者：
BUCALA, R
影响因子：
3.3
作者：
Beishuizen, Albertus;Thijs, Lambertus G
通讯作者：
Thijs, Lambertus G
影响因子：
2.4
作者：
Breuel, KF;Kougias, P;Williams, DL
通讯作者：
Williams, DL
影响因子：
3.3
作者：
Fleshner, M;Goehler, LE;Watkins, LR
通讯作者：
Watkins, LR