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NOD2激动剂与TLR2和TLR4激动剂协同促进血管平滑肌细胞中炎性细胞因子的产生。

NOD2 agonist promotes the production of inflammatory cytokines in VSMC in synergy with TLR2 and TLR4 agonists.

作者信息

Sun Jinghua, Ding Yanchun

机构信息

Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China.

出版信息

ScientificWorldJournal. 2012;2012:607157. doi: 10.1100/2012/607157. Epub 2012 Sep 10.

DOI:10.1100/2012/607157
PMID:22997500
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3446649/
Abstract

OBJECTIVE

To investigate the expression of NOD2 in human VSMCs, its role in the production of inflammatory cytokines in VSMC and the possible interaction of NOD2-mediated signaling pathway with those mediated by TLR2 and TLR4.

METHODS

Human coronary artery smooth muscle cells were stimulated with NOD2 agonist MDP alone or in combination with either TLR2 agonist PAM3 or TLR4 agonist LPSs. The mRNA expression of NOD2 and FGF-2 were measured by RT-PCR. The concentration of IL-8 and TNF-α in the culture supernatants was determined by ELISA. VSMC proliferation ability was analyzed by MTT assay.

RESULTS

MDP up regulated the expression of NOD2 mRNA in VSMC in a time-dependent manner, up regulated the expression of FGF-2 mRNA in VSMC, induced the production of IL-8 and TNF-α, and promoted the proliferation of VSMC. Additionally, MDP synergied with LPS and PAM3 to promote the proliferation of VSMC and induce the production of IL-8 and TNF-α.

CONCLUSION

The activation of NOD2-mediated innate immune signaling pathway can increase the proliferation ability of VSMC and induce the production of inflammatory cytokines in VSMC. It is also shown a synergistic effect with TLR2- and TLR4-mediated signaling pathways in this process.

摘要

目的

研究NOD2在人血管平滑肌细胞(VSMCs)中的表达,其在VSMC中炎性细胞因子产生中的作用以及NOD2介导的信号通路与TLR2和TLR4介导的信号通路之间可能的相互作用。

方法

用人冠状动脉平滑肌细胞单独用NOD2激动剂MDP刺激,或与TLR2激动剂PAM3或TLR4激动剂LPSs联合刺激。通过RT-PCR检测NOD2和FGF-2的mRNA表达。用ELISA测定培养上清液中IL-8和TNF-α的浓度。通过MTT法分析VSMC增殖能力。

结果

MDP以时间依赖性方式上调VSMC中NOD2 mRNA的表达,上调VSMC中FGF-2 mRNA的表达,诱导IL-8和TNF-α的产生,并促进VSMC的增殖。此外,MDP与LPS和PAM3协同促进VSMC的增殖并诱导IL-8和TNF-α的产生。

结论

NOD2介导的天然免疫信号通路的激活可增加VSMC的增殖能力并诱导VSMC中炎性细胞因子的产生。在此过程中还显示出与TLR2和TLR4介导的信号通路具有协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac2/3446649/6b14fef971f8/TSWJ2012-607157.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac2/3446649/a9f0da3184b5/TSWJ2012-607157.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac2/3446649/9f809d19122a/TSWJ2012-607157.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac2/3446649/e13f49202c37/TSWJ2012-607157.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac2/3446649/6b14fef971f8/TSWJ2012-607157.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac2/3446649/a9f0da3184b5/TSWJ2012-607157.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac2/3446649/9f809d19122a/TSWJ2012-607157.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac2/3446649/e13f49202c37/TSWJ2012-607157.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cac2/3446649/6b14fef971f8/TSWJ2012-607157.004.jpg

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