Document Detail


The effects of Th17 cytokines on the inflammatory mediator production and barrier function of ARPE-19 cells.
MedLine Citation:
PMID:  21479174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Th17 cells have emerged as a key factor in the pathogenesis of uveitis as well as other autoimmune disorders. They secrete a number of cytokines including IL-17A, IL-17F and IL-22 and until now the effects of these cytokines on resident cells of the eye were not yet clear. The purpose of this study was to investigate the effects of Interleukin (IL)-17A, IL-17F and IL-22 on the production of inflammatory mediators and barrier function of retinal pigment epithelium cells. We showed that ARPE-19 cells, a spontaneously arisen cell line of retinal pigment epithelium (RPE), constitutively expressed IL-17RC and IL-22R, but not IL-17RA. IL-17A significantly enhanced the production of CXCL8, CCL2, CCL20 and IL-6 by these cells. IL-17F had a similar effect on the production of CXCL8, CCL2 and IL-6 by ARPE-19 cells, but did not influence the expression of CCL20. Both IL-17A and IL-17F significantly decreased the transepithelial electrical resistance (TER) of the ARPE-19 monolayer and increased the diffusion rate of fluorescein isothiocyanate (FITC)-dextran. They also disrupted the distribution of the junction proteins zonula occludens (ZO)-1 and occludin at the interface of adjacent cells. IL-22 did not have a detectable effect on the production of the tested inflammatory mediators by ARPE-19 cells, TER of the ARPE-19 monolayer, the diffusion rate of FITC-dextran or the distribution of ZO-1 and occludin. This study demonstrates that IL-17A and IL-17F, but not IL-22, significantly promoted ARPE-19 cells to secrete inflammatory mediators and compromised the ARPE-19 monolayer barrier function in association with a disrupted distribution of ZO-1 and occludin. These results suggest that both IL-17A and IL-17F may play a role in posterior segment inflammation of the eye.
Authors:
Ying Chen; Peizeng Yang; Fuzhen Li; Aize Kijlstra
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-30
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-04-11     Completed Date:  2011-07-26     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e18139     Citation Subset:  IM    
Affiliation:
Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Blood-Retinal Barrier / drug effects*,  metabolism*
Cell Line
Diffusion / drug effects
Epithelial Cells / drug effects,  metabolism
Humans
Inflammation Mediators / metabolism*
Interleukin-17 / pharmacology*
Interleukins / pharmacology
Membrane Proteins / metabolism
Occludin
Phosphoproteins / metabolism
Receptors, Interleukin / metabolism
Receptors, Interleukin-17 / metabolism
Th17 Cells / cytology,  drug effects,  metabolism*
Zonula Occludens-1 Protein
Chemical
Reg. No./Substance:
0/Inflammation Mediators; 0/Interleukin-17; 0/Interleukins; 0/Membrane Proteins; 0/OCLN protein, human; 0/Occludin; 0/Phosphoproteins; 0/Receptors, Interleukin; 0/Receptors, Interleukin-17; 0/TJP1 protein, human; 0/Zonula Occludens-1 Protein; 0/interleukin-22; 0/interleukin-22 receptor
Comments/Corrections

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