分子大小不同的透明质酸对佛波酯刺激的小鼠软骨细胞的不同作用
Differential effect of molecular size HA in mouse chondrocytes stimulated with PMA.
作者信息
Campo Giuseppe M, Avenoso Angela, Campo Salvatore, D'Ascola Angela, Traina Paola, Calatroni Alberto
机构信息
Department of Biochemical, Physiological and Nutritional Sciences, section of Medical Chemistry, School of Medicine, University of Messina, Policlinico Universitario, Torre Biologica, 5 degrees piano, Via C. Valeria, 98125, Messina, Italy.
出版信息
Biochim Biophys Acta. 2009 Oct;1790(10):1353-67. doi: 10.1016/j.bbagen.2009.07.003. Epub 2009 Jul 14.
BACKGROUND
Hyaluronan (HA) fragments elicit the expression of inflammatory mediators through a mechanism involving the CD44 receptor. This study investigated the effects of HA at different molecular weights on PMA-induced inflammation in mouse chondrocytes.
METHODS
mRNA and related protein levels were measured for CD44, PKCdelta, PKCepsilon, TNF-alpha, IL-1beta, MMP-13, and iNOS in chondrocytes, untreated or PMA treated, with and without the addition of HA. The level of NF-kB activation was also assayed.
RESULTS
CD44, PKCdelta, and PKCepsilon mRNA expression resulted higher than controls in chondrocytes treated with PMA. PMA also induced NF-kB up-regulation and increased TNF-alpha, IL-1beta, MMP-13, and iNOS expression. HA treatment produced different effects: low MW HA up-regulated CD44 expression, increased PKCdelta and PKCepsilon levels, and enhanced inflammation in untreated chondrocytes; while in PMA-treated cells it increased CD44, PKCdelta, PKCepsilon, NF-kB, TNF-alpha, IL-1beta, MMP-13, and iNOS expression and enhanced the effects of PMA; medium MW HA did not exert action; high MW HA had no effect on untreated chondrocytes; however, it reduced PKCdelta, PKCepsilon, NF-kB activation and inflammation in PMA-stimulated cells. Specific CD44 blocking antibody was utilised to confirm CD44 as the target of HA modulation.
GENERAL SIGNIFICANCE
These data suggest that HA via CD44 may modulate inflammation via its different molecular mass.
背景
透明质酸（HA）片段通过涉及CD44受体的机制引发炎症介质的表达。本研究调查了不同分子量的HA对小鼠软骨细胞中佛波酯（PMA）诱导的炎症的影响。
方法
在未处理或经PMA处理的软骨细胞中，添加或不添加HA，测量CD44、蛋白激酶Cδ（PKCδ）、蛋白激酶Cε（PKCε）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、基质金属蛋白酶-13（MMP-13）和诱导型一氧化氮合酶（iNOS）的mRNA及相关蛋白水平。还检测了核因子-κB（NF-κB）的激活水平。
结果
在经PMA处理的软骨细胞中，CD44、PKCδ和PKCε的mRNA表达高于对照组。PMA还诱导NF-κB上调，并增加TNF-α、IL-1β、MMP-13和iNOS的表达。HA处理产生了不同的效果：低分子量HA上调未处理软骨细胞中CD44的表达，增加PKCδ和PKCε水平，并增强炎症；而在经PMA处理的细胞中，它增加CD44、PKCδ、PKCε、NF-κB、TNF-α、IL-1β、MMP-13和iNOS的表达，并增强PMA的作用；中等分子量HA无作用；高分子量HA对未处理软骨细胞无影响；然而，它降低了PMA刺激细胞中PKCδ、PKCε、NF-κB的激活和炎症。使用特异性CD44阻断抗体来确认CD44是HA调节的靶点。
普遍意义
这些数据表明，HA可能通过CD44以其不同的分子量调节炎症。
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