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首页> 外文期刊>Rheumatology >Does HLA-B27 influence the monocyte inflammatory response to lipopolysaccharide?
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Does HLA-B27 influence the monocyte inflammatory response to lipopolysaccharide?

机译：HLA-B27是否会影响单核细胞对脂多糖的炎症反应？

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OBJECTIVES: How human leucocyte antigen B27 (HLA-B27) contributes towards arthritis susceptibility is still unclear, but effects on the response to bacteria unrelated to the classical antigen presenting role of B27 have been suggested. This study investigated whether HLA-B27 modulates the innate response to lipopolysaccharide (LPS), a component shared between all Gram negative bacteria that can trigger reactive arthritis. METHODS: Pools of U937 transfectants expressing either HLA-B27, HLA-A2 or the expression plasmid alone were differentiated with phorbol 12-myristate 13-acetate and stimulated with LPS. Supernatants were analysed for tumour necrosis factor-alpha (TNF-alpha) secretion and the gene expression profiles of unstimulated and LPS-stimulated cells were determined by microarray analysis. Changes in gene expression that are indicative of an unfolded protein response (UPR) were also analysed by quantitative polymerase chain reaction (PCR). RESULTS: TNF-alpha secretion, a biological marker of the inflammatory response to LPS, was not significantly different between U937-B27 and U937-control. No differences in gene expression between unstimulated U937-B27 and U937-control lines were detected. Both U937-control and U937-B27 exhibited a stereotypic response to LPS. Only one gene, OAS2, was differentially expressed by these cell lines, and this was confirmed by quantitative PCR. Analysis of XBP-1 splicing suggested that the UPR is induced following the LPS stimulation, but this increase was seen in all transfectants. CONCLUSIONS: The expression of B27 does not profoundly alter the gene expression following LPS stimulation. Therefore, additional signals, such as those provided by cytokines or intracellular infection, may be required to reveal any influence of B27 expression on the inflammatory response.
机译：目的：人类白细胞抗原B27（HLA-B27）如何促进关节炎易感性尚不清楚，但已提出对与细菌经典反应的B27不相关的细菌反应的影响。这项研究调查了HLA-B27是否调节对脂多糖（LPS）的先天反应，脂多糖是所有可引发反应性关节炎的革兰氏阴性细菌共有的成分。方法：用佛波醇12-肉豆蔻酸酯13-乙酸酯分化表达单独表达HLA-B27，HLA-A2或表达质粒的U937转染子，并用LPS刺激。分析上清液的肿瘤坏死因子-α（TNF-α）分泌，并通过微阵列分析确定未刺激和LPS刺激的细胞的基因表达谱。还通过定量聚合酶链反应（PCR）分析了表示未折叠的蛋白质反应（UPR）的基因表达变化。结果：U937-B27和U937对照之间对LPS的炎症反应的生物学标志物TNF-α分泌没有显着差异。在未刺激的U937-B27和U937对照系之间未检测到基因表达的差异。 U937对照和U937-B27均表现出对LPS的定型反应。这些细胞系仅差异表达OAS2基因，这已通过定量PCR得以证实。对XBP-1剪接的分析表明，LPR刺激后诱导了UPR，但在所有转染子中均可见到这种增加。结论：LPS刺激后B27的表达并没有深刻改变基因表达。因此，可能需要其他信号，例如由细胞因子或细胞内感染提供的信号，以揭示B27表达对炎症反应的任何影响。

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