title: Regulation of inflammation by extracellular acidification and proton-sensing GPCRs.
abstract: 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.
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan. okajima@gunma-u.ac.jp
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
mesh_terms: D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011522:Protons; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C513334:GPR65 protein, human; C486281:GPR68 protein, human; D011522:Protons; D043562:Receptors, G-Protein-Coupled; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Extracellular acidification; GPR4; Inflammation; OGR1; Proton-sensing G protein-coupled receptors (GPCRs); TDAG8