Dust particles-induced intracellular Ca²⁺ signaling and reactive oxygen species in lung fibroblast cell line MRC5.
10.4196/kjpp.2017.21.3.327
- Author:
Dong Un LEE
1
;
Min Jeong JI
;
Jung Yun KANG
;
Sun Young KYUNG
;
Jeong Hee HONG
Author Information
1. Department of Physiology, College of Medicine, Gachon University, Lee Gil Ya Cancer and Diabetes Institute, Incheon 21999, Korea. minicleo@gachon.ac.kr
- Publication Type:Original Article
- Keywords:
Calcium signaling;
Lung fibroblast;
Oxidative stress;
Particulate matter;
Reactive oxygen species
- MeSH:
Antioxidants;
Calcium Signaling;
Cell Line*;
Clotrimazole;
Dust*;
Fibroblasts*;
Fluorescence;
Humans;
Lung Diseases;
Lung*;
Oxidative Stress;
Particulate Matter;
Phospholipases;
Reactive Oxygen Species*
- From:The Korean Journal of Physiology and Pharmacology
2017;21(3):327-334
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
