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构建表达白细胞介素-18 结合蛋白/白细胞介素-4 融合基因的重组腺病毒载体及其对脂多糖刺激的滑膜成纤维细胞的抗炎作用。

Construction of a recombinant adenovirus vector expressing IL-18BP/IL-4 fusion gene and the anti-inflammatory effect induced by this gene on lipopolysaccharide-stimulated synovial fibroblasts.

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, 310003 Hangzhou, China.

出版信息

Inflamm Res. 2010 Feb;59(2):97-104. doi: 10.1007/s00011-009-0072-0. Epub 2009 Nov 22.

DOI:10.1007/s00011-009-0072-0
PMID:20087753
Abstract

OBJECTIVE

To construct a recombinant adenovirus vector for expressing the IL-18 binding protein (IL-18BP)/IL-4 fusion gene and confirm the anti-inflammatory effect of this gene.

MATERIALS AND METHODS

The recombinant virus expressing IL-18BP/IL-4 fusion protein (AD-IL-18BP/IL-4) was constructed. AD-IL-18BP/IL-4 was used to infect synovial fibroblasts (SF). ELISA and Western blot analysis were used to determine the expressions of the proteins IL-4 and IL-18BP. To investigate the protective effects of this vector on rheumatoid arthritis, SF were infected with AD-IL-18BP/IL-4 and stimulated by LPS (1 microg/ml) 4 h later. The expression levels of TNF-alpha, IL-6, IL-8, and IL-18 in the culture supernatant were detected by ELISA and production of PGE2 and NO was estimated. The protein expression of COX-2, iNOS, and NF-kappaB p50 in treated SF was analyzed by Western blot.

RESULTS

AD-IL-18BP/IL-4 can effectively express the IL-18BP/IL-4 fusion protein. The expressions of TNF-alpha, IL-6, IL-8, and IL-18 were significantly inhibited in LPS-stimulated SF after treatment with AD-IL-18BP/IL-4. The production of PGE2 and NO was significantly decreased. Moreover, NF-kappaB p50, COX-2, and iNOS levels in SF were markedly suppressed by AD-IL-18BP/IL-4.

CONCLUSION

AD-IL-18BP/IL-4 can suppress the production and expression of inflammatory cytokines such as COX-2, iNOS, and NF-kappaB in LPS-stimulated SF.

摘要

目的

构建表达白细胞介素-18 结合蛋白（IL-18BP）/白细胞介素-4（IL-4）融合基因的重组腺病毒载体，并证实该基因的抗炎作用。

材料与方法

构建表达 IL-18BP/IL-4 融合蛋白的重组病毒（AD-IL-18BP/IL-4）。AD-IL-18BP/IL-4 感染滑膜成纤维细胞（SF），酶联免疫吸附试验（ELISA）和 Western blot 分析检测 IL-4 和 IL-18BP 蛋白的表达。为了研究该载体对类风湿关节炎的保护作用，SF 感染 AD-IL-18BP/IL-4 后，4 小时用 LPS（1μg/ml）刺激，ELISA 检测细胞培养上清中 TNF-α、IL-6、IL-8 和 IL-18 的表达水平，测定 PGE2 和 NO 的产生。Western blot 分析处理后的 SF 中 COX-2、iNOS 和 NF-κB p50 的蛋白表达。

结果

AD-IL-18BP/IL-4 能有效地表达 IL-18BP/IL-4 融合蛋白。AD-IL-18BP/IL-4 处理后，LPS 刺激的 SF 中 TNF-α、IL-6、IL-8 和 IL-18 的表达明显受到抑制，PGE2 和 NO 的产生明显减少。此外，AD-IL-18BP/IL-4 显著抑制 SF 中 NF-κB p50、COX-2 和 iNOS 水平。

结论

AD-IL-18BP/IL-4 能抑制 LPS 刺激的 SF 中 COX-2、iNOS 和 NF-κB 等炎症细胞因子的产生和表达。

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Expression of interleukin-18, IL-18BP, and IL-18R in serum, synovial fluid, and synovial tissue in patients with rheumatoid arthritis.类风湿关节炎患者血清、滑液及滑膜组织中白细胞介素-18、IL-18结合蛋白和IL-18受体的表达
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PLoS One. 2013;8(3):e58836. doi: 10.1371/journal.pone.0058836. Epub 2013 Mar 13.
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