Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
Cell Signal. 2013 Nov;25(11):2263-71. doi: 10.1016/j.cellsig.2013.07.022. Epub 2013 Jul 31.
Under ischemic and inflammatory circumstances, such as allergic airway asthma, rheumatoid arthritis, atherosclerosis, and tumors, extracellular acidification occurs due to the stimulation of anaerobic glycolysis. An acidic microenvironment has been shown to modulate pro-inflammatory or anti-inflammatory responses, including cyclooxygenase-2 (COX-2) expression, prostaglandin synthesis, and cytokine expression, in a variety of cell types, and thereby to exacerbate or ameliorate inflammation. However, molecular mechanisms underlying extracellular acidic pH-induced actions have not been fully understood. Recent studies have shown that ovarian cancer G protein-coupled receptor 1 (OGR1)-family G protein-coupled receptors (GPCRs) can sense extracellular pH or protons, which in turn stimulates intracellular signaling pathways and subsequent diverse cellular responses. In the present review, I discuss extracellular acidic pH-induced inflammatory responses and related responses in inflammatory cells, such as macrophages and neutrophils, and non-inflammatory cells, such as smooth muscle cells and endothelial cells, focusing especially on proton-sensing GPCRs.
在缺血和炎症等情况下，如过敏性哮喘、类风湿关节炎、动脉粥样硬化和肿瘤，由于无氧糖酵解的刺激，会发生细胞外酸化。酸性微环境已被证明可调节促炎或抗炎反应，包括环氧化酶-2（COX-2）表达、前列腺素合成和细胞因子表达，在多种细胞类型中，并因此加剧或减轻炎症。然而，细胞外酸性 pH 诱导作用的分子机制尚未完全理解。最近的研究表明，卵巢癌 G 蛋白偶联受体 1（OGR1）-家族 G 蛋白偶联受体（GPCR）可以感知细胞外 pH 值或质子，进而刺激细胞内信号通路和随后的多种细胞反应。在本综述中，我讨论了细胞外酸性 pH 值诱导的炎症反应以及炎症细胞（如巨噬细胞和中性粒细胞）和非炎症细胞（如平滑肌细胞和内皮细胞）中的相关反应，特别关注质子感应 GPCR。
