| MCP-1-activated monocytes induce apoptosis in human retinal pigment epithelium. | |
| | |
MedLine Citation:
|
PMID: 21447688 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
PURPOSE: The inflammatory response in age-related macular degeneration (AMD) is characterized by mononuclear leukocyte infiltration of the outer blood-retina barrier formed by the retinal pigment epithelium (RPE). A key mechanistic element in AMD progression is RPE dysfunction and apoptotic cell loss. The purpose of this study was to evaluate whether monocyte chemoattractant protein (MCP)-1-activated monocytes induce human RPE apoptosis and whether Ca(2+) and reactive oxygen species (ROS) are involved in this process. METHODS: A cell-based fluorometric assay was used to measure intracellular Ca(2+) concentrations ([Ca(2+)](i)) in RPE cells loaded with fluorescent Ca(2+) indicator. Intracellular RPE ROS levels were measured by using the 5- and 6-chloromethyl-2',7'-dichlorodihydrofluorescence diacetate acetyl ester (CM-H(2)DCFDA) assay. RPE apoptosis was evaluated by activated caspase-3, Hoechst staining, and apoptosis ELISA. RESULTS: MCP-1-activated human monocytes increased [Ca(2+)](i), ROS levels, and apoptosis in RPE cells, all of which were inhibited by 8-bromo-cyclic adenosine diphosphoribosyl ribose (8-Br-cADPR), an antagonist of cADPR. Although the ROS scavengers pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAC) significantly inhibited ROS production and apoptosis induced by activated monocytes, they did not affect induced Ca(2+) levels. The induced Ca(2+) levels and apoptosis in RPE cells were inhibited by an antibody against cluster of differentiation antigen 14 (CD14), an adhesion molecule expressed by these cells. CONCLUSIONS: These results indicate that CD14, Ca(2+), and ROS are involved in activated monocyte-induced RPE apoptosis and that cADPR contributes to these changes. Understanding the complex interactions among CD14, cADPR, Ca(2+), and ROS may provide new insights and treatments of retinal diseases, including AMD. |
| | |
Authors:
|
Dongli Yang; Susan G Elner; Xun Chen; Matthew G Field; Howard R Petty; Victor M Elner |
Related Documents
:
|
15843208 - Modulation of translation factor's gene expression by histone deacetylase inhibitors in... 21501368 - Phagocytosis of melanized aspergillus conidia by macrophages exerts cytoprotective effe... 21151158 - The distinct role of guanine nucleotide exchange factor vav1 in bcl-2 transcription and... 21252908 - F-box protein 10, an nf-κb-dependent anti-apoptotic protein, regulates trail-induced a... 15466378 - Transgenic mice overexpressing bmp4 develop a fibrodysplasia ossificans progressiva (fo... 20859658 - Application of alpha7 nicotinic acetylcholine receptor agonists in inflammatory disease... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-07-29 |
Journal Detail:
|
Title: Investigative ophthalmology & visual science Volume: 52 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2011 Jul |
Date Detail:
|
Created Date: 2011-08-01 Completed Date: 2011-09-30 Revised Date: 2012-01-02 |
Medline Journal Info:
|
Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
|
Languages: eng Pagination: 6026-34 Citation Subset: IM |
Affiliation:
|
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105-0714, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aged Aged, 80 and over Antibodies / pharmacology Antigens, CD14 / immunology Apoptosis / drug effects, immunology* Calcium / metabolism Calcium Signaling / physiology Cells, Cultured Chemokine CCL2 / immunology*, metabolism Cyclic ADP-Ribose / analogs & derivatives, antagonists & inhibitors, pharmacology Humans Macular Degeneration / immunology*, pathology Middle Aged Monocytes / immunology*, pathology Reactive Oxygen Species / antagonists & inhibitors, metabolism Retinal Pigment Epithelium / immunology*, pathology |
| Grant Support | |
ID/Acronym/Agency:
|
EY019986/EY/NEI NIH HHS; P30EY07003/EY/NEI NIH HHS; R01EY009441/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/8-bromo-cyclic-ADP-ribose; 0/Antibodies; 0/Antigens, CD14; 0/CCL2 protein, human; 0/Chemokine CCL2; 0/Reactive Oxygen Species; 119340-53-3/Cyclic ADP-Ribose; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Sustained antibiotic release from an intraocular lens-hydrogel assembly for cataract surgery.
Next Document: Automated perimetry: using gaze-direction data to improve the estimate of scotoma edges.