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人免疫调节细胞中过氧化物酶体增殖物激活受体γ的功能基因组学

Functional genomics of PPAR-gamma in human immunomodulatory cells.

作者信息

Kaul Deepak, Anand Paras K, Khanna Amit

机构信息

Molecular Biology Unit, Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.

出版信息

Mol Cell Biochem. 2006 Oct;290(1-2):211-5. doi: 10.1007/s11010-006-9169-8. Epub 2006 Apr 22.

Abstract

Keeping in view the fact that peroxisome-proliferators activated receptors-PPARs (alpha,gamma) play a crucial role in atherogenic inflammation, the present study was addressed to explore as to how selective and specific PPAR-gamma gene silencing within human mononuclear cells affects genes involved in lipid metabolism and innate immune process. Such a study revealed that with respect to control cells, the PPAR-gamma knock-out cells exhibited significant reduction in the expression of genes coding for PPAR- alpha, CD-36, LDL-R as well as significant increase in the expression of genes coding for IL-4, IL-8, IFN-gamma, CX3CR1, hTERT. However, the expression of genes coding for LXR-alpha and Receptor-C( k ) could not be detected in PPAR-gamma knock-out cells. Based on these results, we propose that PPAR-gamma gene has the inherent capacity to influence the lipid mediated inflammation process in atherosclerotic lesions.

摘要

鉴于过氧化物酶体增殖物激活受体(PPARs,α、γ)在动脉粥样硬化炎症中起关键作用,本研究旨在探讨人类单核细胞内PPAR-γ基因的选择性和特异性沉默如何影响参与脂质代谢和固有免疫过程的基因。这样一项研究表明,与对照细胞相比,PPAR-γ基因敲除细胞中编码PPAR-α、CD-36、低密度脂蛋白受体(LDL-R)的基因表达显著降低,而编码白细胞介素-4(IL-4)、白细胞介素-8(IL-8)、干扰素-γ(IFN-γ)、CX3C趋化因子受体1(CX3CR1)、人端粒酶逆转录酶(hTERT)的基因表达显著增加。然而,在PPAR-γ基因敲除细胞中未检测到编码肝X受体-α(LXR-α)和C型受体(k)的基因表达。基于这些结果,我们提出PPAR-γ基因具有影响动脉粥样硬化病变中脂质介导的炎症过程的内在能力。

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