Korean J Physiol Pharmacol 2017; 21(3): 327-334
Published online May 1, 2017 https://doi.org/10.4196/kjpp.2017.21.3.327
Copyright © Korean J Physiol Pharmacol.
Dong Un Lee1,#, Min Jeong Ji1,#, Jung Yun Kang2,#, Sun Young Kyung3, and Jeong Hee Hong1,*
1Department of Physiology, College of Medicine, Gachon University, Lee Gil Ya Cancer and Diabetes Institute, Incheon 21999, 2Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 03722, 3Division of Pulmonary, Allergy and Critical Care Medicine, Gachon University, Gil Medical Center, Incheon 21565, Korea
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established Ca2+ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular Ca2+ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular Ca2+ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than 10 µm, induced intracellular Ca2+ signaling, which was mediated by extracellular Ca2+. The PM10-mediated intracellular Ca2+ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.
Keywords: Calcium signaling, Lung fibroblast, Oxidative stress, Particulate matter, Reactive oxygen species
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