氨基胍对人骨关节炎滑膜组织和软骨培养物中白细胞介素1β产生的下调作用。

Down regulation of interleukin 1beta production in human osteoarthritic synovial tissue and cartilage cultures by aminoguanidine.

作者信息

Shirazi I, Yaron I, Wollman Y, Blum M, Chernihovsky T, Judovich R, Iaina A, Yaron M

机构信息

Department of Rheumatology, Ichilov Hospital, Tel Aviv-Souraski Medical Centre, 6 Weizmann Street, Tel Aviv 64239, Israel.

出版信息

Ann Rheum Dis. 2001 Apr;60(4):391-4. doi: 10.1136/ard.60.4.391.

DOI:10.1136/ard.60.4.391

PMID:11247871

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1753608/

Abstract

OBJECTIVE

To evaluate the effect of aminoguanidine (AG) on de novo interleukin 1beta (IL1beta), nitric oxide (NO), and interleukin 1 receptor antagonist (IL1ra) production by osteoarthritic human synovial tissue and articular cartilage cultures.

METHODS

Synovial tissue and cartilage, obtained during surgery from 29 patients undergoing total knee or hip replacement for osteoarthritis, were cut into small pieces and cultured in the presence or absence of lipopolysaccharide (LPS) and test materials. IL1beta, IL1ra, and NO were determined in culture media. The inducible nitric oxide synthase inhibitor, AG, was added to cultures in various concentrations (0.3-3 mmol/l).

RESULTS

In synovial tissue cultures AG (0.3, 1, and 3 mmol/l) decreased LPS (1 microg/ml) stimulated IL1beta and NO release in the media in a dose dependent manner (p<0.05 at 1 mmol/l and p<0.05 at 0.3 mmol/l, respectively). In articular cartilage cultures AG (0.3, 1, and 3 mmol/l) decreased LPS (1 microg/ml) stimulated IL1beta and NO release in the media in a dose dependent manner (p<0.05 at 1 mmol/l and p<0.01 at 0.3 mmol/l, respectively). Hydrocortisone (5 microg/ml) also significantly decreased LPS stimulated IL1beta release in media of synovial tissue and cartilage cultures and NO in media of synovial cultures. AG (0.3, 1, and 3 mmol/l) decreased LPS (1 microg/ml) stimulated IL1ra levels in media of synovial tissue cultures in a dose dependent manner (p<0.05 at 1 mmol/l) but increased LPS (1 microg/ml) stimulated IL1ra release in media of cartilage cultures (p<0.01 at 3 mmol/l). The NO donor, nitroprusside (10, 30, 100, and 300 microg/ml) stimulated IL1beta release in media of synovial tissue cultures in a dose dependent manner (p<0.01 at 100 microg/ml). AG and nitroprusside at the concentrations used had no toxic effect on human synovial cells.

CONCLUSIONS

NO synthase inhibitors may modulate osteoarthritis and articular inflammatory processes not only by decreasing NO synthesis but also by their effects on ILbeta and IL1ra production.

摘要

目的

评估氨基胍（AG）对骨关节炎患者滑膜组织和关节软骨培养物中白细胞介素1β（IL1β）、一氧化氮（NO）和白细胞介素1受体拮抗剂（IL1ra）从头合成的影响。

方法

从29例行全膝关节或髋关节置换术治疗骨关节炎的患者手术中获取滑膜组织和软骨，切成小块，在有或无脂多糖（LPS）及测试材料的情况下进行培养。测定培养基中的IL1β、IL1ra和NO。将诱导型一氧化氮合酶抑制剂AG以不同浓度（0.3 - 3 mmol/L）加入培养物中。

结果

在滑膜组织培养中，AG（0.3、1和3 mmol/L）以剂量依赖性方式降低LPS（1 μg/ml）刺激的培养基中IL1β和NO释放（1 mmol/L时p<0.05，0.3 mmol/L时p<0.05）。在关节软骨培养中，AG（0.3、1和3 mmol/L）以剂量依赖性方式降低LPS（1 μg/ml）刺激的培养基中IL1β和NO释放（1 mmol/L时p<0.05，0.3 mmol/L时p<0.01）。氢化可的松（5 μg/ml）也显著降低滑膜组织和软骨培养物培养基中LPS刺激的IL1β释放以及滑膜培养物培养基中的NO。AG（0.3、1和3 mmol/L）以剂量依赖性方式降低滑膜组织培养物培养基中LPS（1 μg/ml）刺激的IL1ra水平（1 mmol/L时p<0.05），但增加软骨培养物培养基中LPS（1 μg/ml）刺激的IL1ra释放（3 mmol/L时p<0.01）。NO供体硝普钠（10、30、100和300 μg/ml）以剂量依赖性方式刺激滑膜组织培养物培养基中IL1β释放（100 μg/ml时p<0.01）。所用浓度的AG和硝普钠对人滑膜细胞无毒性作用。