Control of cell migration and inflammatory mediators production by CORM-2 in osteoarthritic synoviocytes.
Control of cell migration and inflammatory mediators production by CORM-2 in osteoarthritic synoviocytes.
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DOI：
10.1371/journal.pone.0024591
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Alcaraz MJ
中科院分区：
文献类型：
--
作者：
García-Arnandis I;Guillén MI;Gomar F;Castejón MA;Alcaraz MJ
骨关节炎(OA)是最常见的退行性关节疾病。炎症的滑膜细胞有助于在骨性关节炎期间释放炎症和分解代谢介质，导致关节组织的破坏。我们以前已经证明，CO释放分子在动物模型和骨关节炎软骨细胞中发挥抗炎作用。我们研究了CORM-2调节人骨性关节炎滑膜细胞迁移的能力，以及在骨性关节炎关节炎症和分解代谢过程中趋化因子和其他介质的产生。在CORM-2存在或不存在的情况下，用IL-1β刺激OA滑膜细胞。迁移试验使用Transwell小室进行。用定量聚合酶链式反应分析基因表达，用Western Blot和ELISA法分析蛋白表达。CORM-2可抑制骨性关节炎滑膜细胞的增殖和迁移，减少IL-8、CCL2、CCL20、基质金属蛋白酶(MMP1)和MMP3的表达，减少氧化应激的产生。我们发现CORM-2降低了细胞外信号调节的K1/2、c-Jun氨基末端Kase1/2的磷酸化，程度较小的是p38。我们的结果还表明，CORM-2显著降低了核因子-κB和激活蛋白-1的激活，从而调节了滑膜细胞中趋化因子和基质金属蛋白酶的转录。CORM-2可以下调一些与骨性关节炎滑膜炎和关节退变相关的滑膜细胞功能。这些结果支持了这类药物在炎症和退行性疾病条件下开发新的治疗策略的兴趣。
Osteoarthritis (OA) is the most widespread degenerative joint disease. Inflamed synovial cells contribute to the release of inflammatory and catabolic mediators during OA leading to destruction of articular tissues. We have shown previously that CO-releasing molecules exert anti-inflammatory effects in animal models and OA chondrocytes. We have studied the ability of CORM-2 to modify the migration of human OA synoviocytes and the production of chemokines and other mediators sustaining inflammatory and catabolic processes in the OA joint. OA synoviocytes were stimulated with interleukin(IL)-1β in the absence or presence of CORM-2. Migration assay was performed using transwell chambers. Gene expression was analyzed by quantitative PCR and protein expression by Western Blot and ELISA. CORM-2 reduced the proliferation and migration of OA synoviocytes, the expression of IL-8, CCL2, CCL20, matrix metalloproteinase(MMP)-1 and MMP-3, and the production of oxidative stress. We found that CORM-2 reduced the phosphorylation of extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase1/2 and to a lesser extent p38. Our results also showed that CORM-2 significantly decreased the activation of nuclear factor-κB and activator protein-1 regulating the transcription of chemokines and MMPs in OA synoviocytes. A number of synoviocyte functions relevant in OA synovitis and articular degradation can be down-regulated by CORM-2. These results support the interest of this class of agents for the development of novel therapeutic strategies in inflammatory and degenerative conditions.
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滑膜巨噬细胞和巨噬细胞产生的细胞因子在驱动聚集蛋白聚糖酶、基质金属蛋白酶和骨关节炎中其他破坏性和炎症反应中的作用。
影响因子：
4.9
作者：
Bondeson J;Wainwright SD;Lauder S;Amos N;Hughes CE
通讯作者：
Hughes CE
DOI：
10.1186/ar149
发表时间：
2001
期刊：
Arthritis research
影响因子：
--
作者：
Hayashida K;Nanki T;Girschick H;Yavuz S;Ochi T;Lipsky PE
通讯作者：
Lipsky PE
影响因子：
7.5
作者：
Chevalier, X
通讯作者：
Chevalier, X
影响因子：
5.5
作者：
Guillen, M. I.;Megias, J.;Alcaraz, M. J.
通讯作者：
Alcaraz, M. J.
影响因子：
3.9
作者：
Kawashiri, Shin-Ya;Kawakami, Atsushi;Eguchi, Katsumi
通讯作者：
Eguchi, Katsumi