The aim of this study was to evaluate the effects of the LL-37, HNP-1 and HBD2/3 peptides on cytokine andMMPproduction in human polymorphonuclear cells, mononuclear cells and chondrocytes. The levels of cytokines in supernatants from mononuclear and polymorphonuclear cell cultures were measured with a cytometric bead array by flow cytometry. Likewise, the levels of metalloproteinase/MMP-1, 3, and 13 were measured in supernatants from chondrocyte cultures using an ELISA. The expression of RANKL on lymphocytes was analyzed by flow cytometry.We observed increased levels of TNF-α, IL-6 and IL-10 in mononuclear and polymorphonuclear cell cultures stimulated with HBD-2/3.We also observed increased levels of IFN-γ, IL-10, and IL-6 in mononuclear cell cultures stimulated with HNP-1, and increased IL-6 levels were observed in polymorphonuclear cell cultures exposed to HNP-1. We also found that the MMP-1 level increased in the chondrocyte cultures stimulated with HBD-3, whereas the MMP-1 level was decreased in cultures exposed to LL-37. The present report is the first study to determine that HNP-1and HBD2/3 promote the secretion of pro-inflammatory cytokines by polymorphonuclear and mononuclear cells and the secretion of MMP by chondrocytes, whereas LL-37 diminishes MMP1 secretion. Our results suggest that HBD-2/3 and HNP1 might play a pathological role in rheumatoid arthritis, while LL-37 might have a protective role.

中文翻译：

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LL-37，HNP-1和HBD2 / 3调节人原代细胞培养物中细胞因子TNF-α，IL-6，IFN-γ，IL-10和MMP1的分泌。

这项研究的目的是评估LL-37，HNP-1和HBD2 / 3肽对人多形核细胞，单核细胞和软骨细胞中细胞因子和MMP产生的影响。通过流式细胞术用细胞计数珠阵列测量来自单核和多形核细胞培养物的上清液中的细胞因子水平。同样地，使用ELISA在来自软骨细胞培养物的上清液中测量金属蛋白酶/ MMP-1、3和13的水平。用流式细胞仪分析了RANKL在淋巴细胞上的表达，观察到HBD-2 / 3刺激的单核和多形核细胞培养物中TNF-α，IL-6和IL-10的水平升高，也观察到IFN-α的水平升高。 HNP-1刺激的单核细胞培养物中的γ，IL-10和IL-6，并且在暴露于HNP-1的多形核细胞培养物中观察到IL-6水平升高。我们还发现，在HBD-3刺激的软骨细胞培养物中，MMP-1水平升高，而在暴露于LL-37的培养物中，MMP-1水平降低。本报告是第一个确定HNP-1和HBD2 / 3促进多形核和单核细胞促炎细胞因子的分泌和软骨细胞分泌MMP的研究，而LL-37减少MMP1的分泌。我们的结果表明，HBD-2 / 3和HNP1可能在类风湿关节炎中起病理作用，而LL-37可能起保护作用。本报告是第一个确定HNP-1和HBD2 / 3促进多形核和单核细胞促炎细胞因子的分泌和软骨细胞分泌MMP的研究，而LL-37减少MMP1的分泌。我们的结果表明，HBD-2 / 3和HNP1可能在类风湿关节炎中起病理作用，而LL-37可能起保护作用。本报告是第一个确定HNP-1和HBD2 / 3促进多形核和单核细胞促炎细胞因子的分泌和软骨细胞分泌MMP的研究，而LL-37减少MMP1的分泌。我们的结果表明，HBD-2 / 3和HNP1可能在类风湿关节炎中起病理作用，而LL-37可能起保护作用。