Document Detail

Mature dendritic cell suppression by IL-1 receptor antagonist on retinal pigment epithelium cells.
MedLine Citation:
PMID:  23532521     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To determine whether retinal pigment epithelial (RPE) cells can inhibit mature dendritic cells (mDCs).
METHODS: Cultured RPE cells were established from C57BL/6 mice. DCs were established from bone marrow cells of normal mice, and mDCc were induced by culture in medium containing granulocyte macrophage-colony-stimulating factor (GM-CSF) and IL-4 in the presence of lipopolysaccharide and TNF-α. Activation of mDCs was assessed by a proliferation assay and ELISA to measure the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-12p40). Expression of major histocompatibility complex (MHC) class II, CD11c, and costimulatory molecules such as CD80, CD86, programmed cell death 1 ligand 1 (PD-L1), and PD-L2 on mDCs or RPE-exposed mDCs was evaluated by immune staining and flow cytometry. Production of IL-1 receptor antagonist (IL-1Ra) by RPE cells was evaluated by oligonucleotide microarray or ELISA. Anti-IL-1Ra neutralizing antibodies or RPE cells from IL-1Ra knockout donors were used for the assay.
RESULTS: Cultured RPE cells greatly suppressed the activation of mDCs, especially the production of pro-inflammatory cytokines, and the expression of cell-surface molecules. Moreover, RPE cells significantly suppressed mixed lymphocyte reactions by mDCs. In an examination of immunoregulatory candidate molecules, RPE cells expressed much higher levels of IL-1Ra as compared with control cells, and RPE cells pretreated with recombinant TNF-α and/or IL-1β produced high levels of IL-1Ra. RPE cells in the presence of anti-IL-1Ra antibodies, but not other candidate factors, failed to suppress activation by mDCs. In addition, RPE cells from IL-1Ra null donors failed to suppress mDC activation.
CONCLUSIONS: Our results suggest that ocular resident cells can produce pro-inflammatory cytokine antagonist that suppresses antigen-presenting cell activation.
Sunao Sugita; Yuko Kawazoe; Ayano Imai; Yoshihiko Usui; Yoichiro Iwakura; Kikuo Isoda; Masataka Ito; Manabu Mochizuki
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-05-07
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-08     Completed Date:  2013-07-10     Revised Date:  2013-08-08    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3240-9     Citation Subset:  IM    
Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine and Dental Sciences, Tokyo, Japan.
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MeSH Terms
Antigen Presentation
Bone Marrow Cells / drug effects
Cell Differentiation
Cell Proliferation
Cells, Cultured
Coculture Techniques
Cytokines / metabolism
Dendritic Cells / cytology*
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Fluorescent Antibody Technique, Indirect
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Interleukin 1 Receptor Antagonist Protein / physiology*
Lipopolysaccharides / pharmacology
Lymphocyte Culture Test, Mixed
Mice, Inbred BALB C
Mice, Inbred C57BL
Retinal Pigment Epithelium / cytology,  metabolism*
T-Lymphocytes / cytology
Reg. No./Substance:
0/Cytokines; 0/Il1rn protein, mouse; 0/Interleukin 1 Receptor Antagonist Protein; 0/Lipopolysaccharides; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

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