ANP inhibits LPS-induced stimulation of rat microglial cells by suppressing NF-kappaB and AP-1 activations.
ANP inhibits LPS-induced stimulation of rat microglial cells by suppressing NF-kappaB and AP-1 activations.
复制标题
DOI：
10.1016/j.bbrc.2006.09.034
复制
发表时间：
2006-11
影响因子：
3.1
通讯作者：
Naoki Moriyama;M. Taniguchi;Kanako Miyano;M. Miyoshi;Tatsuo Watanabe
中科院分区：
文献类型：
--
作者：
Naoki Moriyama;M. Taniguchi;Kanako Miyano;M. Miyoshi;Tatsuo Watanabe
心钠素(ANP)可抑制脂多糖(LPS)诱导巨噬细胞产生一氧化氮(NO)和促炎细胞因子[包括白介素1(IL-1)]等炎症因素。在本研究中，我们使用原代培养的大鼠脑巨噬细胞样细胞(即小胶质细胞)，研究心钠素与其受体结合是否通过影响促炎转录因子NF-κB和AP-1的激活来抑制内毒素诱导的小胶质细胞激活。通过检测NO和IL-1的产生以及细胞形态的变化来评估内毒素对小胶质细胞的激活作用。我们的RT-PCR研究表明，大鼠小胶质细胞表达ANP受体(A、B和C型)和ANP分子的mRNAs。内毒素(100 ng/ml)刺激的小胶质细胞亚硝酸盐(NO的一种相对稳定的代谢物)和IL-1浓度增加，IL-1mRNA表达增加，形态由阿米巴状变为多极(多数为双极，有时也有三极)杆状。这些效应均被心钠素(10−6M或以下)显著抑制。NP受体拮抗剂HS-142-1(100 ng/ml)可阻断ANP对内毒素诱导的亚硝酸盐反应的抑制作用。NF-κB和AP-1活性在内毒素刺激的小胶质细胞中显著增强，这种增强作用可被心钠素(10−6M)显著抑制。这些结果提示，心钠素通过激活小胶质细胞心钠素受体抑制脂多糖刺激的小胶质细胞活性，从而抑制核因子-κB和AP-1。
Atrial natriuretic peptide (ANP) contributes to the inhibition of such causes of inflammation as the lipopolysaccharide (LPS)-induced productions of nitric oxide (NO) and proinflammatory cytokines [including interleukin-1 (IL-1)] in macrophages. In the present study we used primary cultures of rat brain macrophage-like cells (i.e., microglial cells) to investigate whether ANP binding to its receptors inhibits LPS-induced microglial activation via effects on the activation of the proinflammatory transcription factors NF-κB and AP-1. The productions of NO and IL-1, as well as morphological changes, were examined to assess LPS-induced activation of microglial cells. Our RT-PCR study revealed that rat microglial cells express the mRNAs for ANP receptors (types A, B, and C) and that for the ANP molecule. LPS (100ng/ml)-stimulated microglial cells showed increases in nitrite (a relatively stable metabolite of NO) and IL-1 concentrations, and in the expression of IL-1 mRNA, as well as a morphological change from an amoeboid shape to a multipolar (mostly bipolar, but sometimes tripolar) rod shape. These effects were all significantly inhibited by treatment with ANP (at 10−6M or less). The inhibition by ANP of the LPS-induced nitrite response was abrogated by a NP-receptor antagonist, HS-142-1 (100ng/ml). NF-κB and AP-1 activities were enhanced in LPS-stimulated microglial cells, and these enhancements were significantly suppressed by ANP (10−6M). These results suggest that ANP inhibits LPS-stimulated activities in microglial cells through activation of microglial ANP receptors, leading to inhibitions of NF-κB and AP-1.