RRC ID 55974
Author Klinngam W, Fu R, Janga SR, Edman MC, Hamm-Alvarez SF.
Title Cathepsin S Alters the Expression of Pro-Inflammatory Cytokines and MMP-9, Partially through Protease-Activated Receptor-2, in Human Corneal Epithelial Cells.
Journal Int J Mol Sci
Abstract Cathepsin S (CTSS) activity is increased in tears of Sjögren's syndrome (SS) patients. This elevated CTSS may contribute to ocular surface inflammation. Human corneal epithelial cells (HCE-T cells) were treated with recombinant human CTSS at activity comparable to that in SS patient tears for 2, 4, 8, and 24 h. Acute CTSS significantly increased HCE-T cell gene and protein expression of interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) from 2 to 4 h, while matrix metalloproteinase 9 (MMP-9), CTSS, and protease-activated receptor-2 (PAR-2) were increased by chronic CTSS (24 h). To investigate whether the increased pro-inflammatory cytokines and proteases were induced by CTSS activation of PAR-2, HCE-T cells were transfected with PAR-2 siRNA, reducing cellular PAR-2 by 45%. Cells with reduced PAR-2 expression showed significantly reduced release of IL-6, TNF-α, IL-1β, and MMP-9 into culture medium in response to acute CTSS, while IL-6, TNF-α, and MMP-9 were reduced in culture medium, and IL-6 and MMP-9 in cell lysates, after chronic CTSS. Moreover, cells with reduced PAR-2 expression showed reduced ability of chronic CTSS to induce gene expression of pro-inflammatory cytokines and proteases. CTSS activation of PAR-2 may represent a potential therapeutic target for amelioration of ocular surface inflammation in SS patients.
Volume 19(11)
Published 2018-11-9
DOI 10.3390/ijms19113530
PII ijms19113530
PMID 30423938
PMC PMC6274678
MeSH Cathepsins / metabolism* Cathepsins / pharmacology Culture Media Cytokines / genetics Cytokines / metabolism* Epithelial Cells / metabolism* Epithelium, Corneal / pathology* Gene Expression Regulation / drug effects Humans Inflammation Mediators / metabolism* Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism* Models, Biological Receptor, PAR-2 / genetics Receptor, PAR-2 / metabolism* Signal Transduction / drug effects
IF 3.687
Human and Animal Cells HCE-T(RCB2280)