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首页> 外文期刊>Cytokine >Low extracellular pH stimulates the production of IL-1β by human monocytes
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Low extracellular pH stimulates the production of IL-1β by human monocytes

机译：低细胞外pH刺激人单核细胞产生IL-1β

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摘要

The development of acidic environments is a hallmark of inflammatory processes of different etiology. We have previously shown that transient exposure to acidic conditions, similar to those encountered in vivo, induces the activation of neutrophils and the phenotypic maturation of dendritic cells. We here report that extracellular acidosis (pH 6.5) selectively stimulates the production and the secretion of IL-1β by human monocytes without affecting the production of TNF-α, IL-6 and the expression of CD40, CD80, CD86, and HLA-DR. Stimulation of IL-1β production by pH 6.5-treated monocytes was shown to be dependent on caspase-1 activity, and it was also observed using peripheral blood mononuclear cells instead of isolated monocytes. Contrasting with the results in monocytes, we found that pH 6.5 did not stimulate any production of IL-1β by macrophages. Changes in intracellular pH seem to be involved in the stimulation of IL-1β production. In fact, monocytes cultured at pH 6.5 undergo a fall in the values of intracellular pH while the inhibitor of the Na+/H+ exchanger, 5-(N-ethyl- N-isopropyl)amiloride induced both, a decrease in the values of intracellular pH and the stimulation of IL-1β production. Real time quantitative PCR assays indicated that monocytes cultured either at pH 6.5 or in the presence of 5-(N-ethyl- N-isopropyl)amiloride expressed higher levels of pro-IL-1β mRNA suggesting that low values of intracellular pH enhance the production of IL-1β, at least in part, by stimulating the synthesis of its precursor.
机译：酸性环境的发展是不同病因的炎症过程的标志。先前我们已经证明，与体内所遇到的情况类似，短暂暴露于酸性条件下会诱导嗜中性粒细胞的活化和树突状细胞的表型成熟。我们在此报告细胞外酸中毒（pH 6.5）选择性刺激人单核细胞的产生和分泌IL-1β，而不影响TNF-α，IL-6的产生以及CD40，CD80，CD86和HLA-DR的表达。 pH 6.5处理的单核细胞刺激IL-1β产生取决于caspase-1活性，并且还观察到使用外周血单核细胞代替分离的单核细胞。与单核细胞的结果相反，我们发现pH 6.5不会刺激巨噬细胞产生IL-1β。细胞内pH的改变似乎与IL-1β产生的刺激有关。实际上，在pH 6.5下培养的单核细胞的细胞内pH值会下降，而Na + / H +交换子抑制剂5-（N-乙基-N-异丙基）阿米洛利会同时诱导这两种情况，从而降低细胞内pH值和刺激IL-1β的产生。实时定量PCR分析表明，在pH 6.5或5-（N-乙基-N-异丙基）阿米洛利存在下培养的单核细胞表达更高水平的pro-IL-1βmRNA，这表明低的细胞内pH值可提高产量至少部分地通过刺激其前体的合成来抑制IL-1β的表达。

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