RRC ID 62879
Author Tsai MH, Chi MC, Hsu JF, Lee IT, Lin KM, Fang ML, Lee MH, Lee CW, Liu JF.
Title Urban Particulate Matter Enhances ROS/IL-6/COX-II Production by Inhibiting MicroRNA-137 in Synovial Fibroblast of Rheumatoid Arthritis.
Journal Cells
Abstract BACKGROUND:Rheumatoid arthritis (RA) has been associated with air pollution, possibly due to the augmentation of inflammatory effects. In this study, we aimed to determine the roles of inflammatory pathways and microRNA involved in the pathogenesis of RA fibroblast-like synoviocytes (FLS) inflammation induced by particulate matter.
METHODS:The inflammatory mediators, messenger RNAs, microRNAs and their interrelationships were investigated using western blotting, QPCR, ELISA and immunohistochemistry.
RESULTS:Particulate matter (PMs) induced an increase in the expression of interleukin-6 (IL-6) and cyclooxygenase-II (COX-II) in RA-FLS and microRNA-137 was found definitely to mediate the inflammatory pathways. PMs-induced generation of reactive oxygen species (ROS) in RA-FLS was attenuated by pretreatment with antioxidants. Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38 and JNK, followed by downregulation of microRNA-137. In vivo studies, the joints of rats exposed to PMs revealed synovial fibroblast inflammation under pathologic examination and the expressions of IL-6 and COX-II were obviously increased. PMs exposure results in activated ROS-mediated mitogen-activated protein kinase (MAPK) signaling pathways and cause increased IL-6 and COX-II through downregulation of hsa-miRNA-137, which lead to inflammation and RA exacerbation.
CONCLUSIONS:microRNA-137 plays an important role in PMs-induced RA acute exacerbation through MAPK signaling pathways and IL-6/COX-II activation. Targeting these mechanisms can potentially be used to develop new therapeutic strategies and prevention of RA inflammation in the future.
Volume 9(6)
Published 2020-6-2
DOI 10.3390/cells9061378
PII cells9061378
PMID 32498294
PMC PMC7348867
MeSH Animals Arthritis, Rheumatoid / genetics Arthritis, Rheumatoid / pathology* Base Sequence Cities Cyclooxygenase 2 / metabolism* Disease Models, Animal Fibroblasts / metabolism* Fibroblasts / pathology Humans Interleukin-6 / metabolism* MAP Kinase Signaling System MicroRNAs / genetics MicroRNAs / metabolism* Models, Biological Particulate Matter / adverse effects* Reactive Oxygen Species / metabolism* Synoviocytes / metabolism* Synoviocytes / pathology
IF 4.366
Human and Animal Cells MH7A(RCB1512)