Role of toll-like receptor 4 on lupus lung injury and atherosclerosis in LPS-challenge ApoE⁻/⁻ mice.
Role of toll-like receptor 4 on lupus lung injury and atherosclerosis in LPS-challenge ApoE⁻/⁻ mice.
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DOI：
10.1155/2013/476856
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发表时间：
2013
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Ni JQ;Ouyang Q;Lin L;Huang Z;Lu H;Chen X;Lin H;Wang Z;Xu D;Zhang Y
为了研究toll样受体4（TLR 4）在肺损伤和动脉粥样硬化中的病理机制，分别对ApoE−/−或野生型小鼠腹腔内给予生理盐水、脂多糖（LPS）或LPS + TAK-242（TLR 4抑制剂），每周两次，持续4周。ELISA法检测血清抗核抗体（ANA）、抗双链DNA抗体（anti-dsDNA）、细胞因子γ干扰素（IFN-γ）、肿瘤坏死因子（TNF-α）、白细胞介素1 β（IL-1β）水平。采用苏木精-伊红（HE）和Perl染色观察肺病理形态学，HE染色观察动脉粥样硬化。免疫荧光双标法检测巨噬细胞中TLR 4的表达。免疫组化法检测TLR 4、核因子-κ B p65（NF-κB p65）和肿瘤坏死因子家族的B细胞活化因子（BAFF）的蛋白表达。结果表明，两种基因型小鼠血清自身抗体（ANA和抗dsDNA）、细胞因子（IFN-γ、TNF-α、IL-1β）、肺部炎症和头臂动脉内膜中层厚度均明显增加，野生型小鼠增加程度较轻。LPS和TAK-242联合给药可缓解这些变化。机制上，TLR 4、NF-κB和BAFF的上调参与其中。结论：巨噬细胞内TLR 4/NF-κB/BAFF可能是导致肺损伤和动脉粥样硬化的一条共同的自身免疫途径。TLR 4信号将成为动脉粥样硬化和免疫介导的肺损伤的治疗靶点。
To investigate the pathologic mechanisms of toll-like receptor 4 (TLR4) in lung injury and atherosclerosis, ApoE−/− or wild-type mice were intraperitoneally administered saline, lipopolysaccharides (LPS), or LPS plus TAK-242 (TLR4 inhibitor), respectively, twice a week for 4 weeks. Serum autoantibody of antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and cytokines of interferon-gamma (IFN-γ), tumor necrosis factor (TNF-α), and interleukin-1 (IL-1β) were assessed by ELISA. Hematoxylin and eosin (HE) and Perl's stains for lung pathomorphology as well as HE staining for atherosclerosis were employed. TLR4 in macrophages was detected by double immunofluorescent staining. While protein expressions of TLR4, nuclear factor-kappa B p65 (NF-κB p65), and B cell activating factor belonging to the TNF family (BAFF) were examined by immunohistochemistry. We found that serum autoantibody (ANA and anti-dsDNA), cytokines (IFN-γ, TNF-α, IL-1β), lung inflammation, and intima-media thickness in brachiocephalic artery were obviously increased after LPS challenge in both genotypes, but to a lesser extent in wild-type strains. And those alterations were alleviated by coadministration of LPS and TAK-242. Mechanistically, upregulation of TLR4, NF-κb, and BAFF was involved. We concluded that TLR4/NF-κb/BAFF in macrophages might be a possible common autoimmune pathway that caused lung injury and atherosclerosis. TLR4 signal will be a therapeutic target in atherosclerosis and immune-mediated lung injury.
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DOI：
10.1152/ajplung.00013.2008
发表时间：
2008-05-01
影响因子：
4.9
作者：
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通讯作者：
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影响因子：
3.7
作者：
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影响因子：
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作者：
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影响因子：
4
作者：
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通讯作者：
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DOI：
10.1111/j.1742-7843.2010.00617.x
发表时间：
2010-12-01
影响因子：
3.1
作者：
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