Document Detail


Aminoimidazole carboxamide ribonucleotide ameliorates experimental autoimmune uveitis.
MedLine Citation:
PMID:  22562518     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To investigate the anti-inflammatory effect of an adenosine monophosphate (AMP) analog, aminoimidazole carboxamide ribonucleotide (AICAR), in experimental autoimmune uveoretinitis (EAU).
METHODS: C57BL/6 mice were injected daily with AICAR (200 mg/kg, intraperitoneally [IP]) from day 0, the day of interphotoreceptor retinoid-binding protein (IRBP) immunization, until day 21. The severity of uveitis was assessed clinically and histopathologically. T-cell proliferation and cytokine production of IFN-γ, IL-17, and IL-10 in response to IRBP stimulation were determined. In addition, regulatory T-cell (Treg) populations were measured. Co-stimulatory molecule expression (CD40, 80, 86, and I-Ab) on dendritic cells (DCs) in EAU and on bone marrow-derived dendritic cells (BMDCs) treated with AICAR was measured.
RESULTS: AICAR treatment significantly reduced clinical and histologic severity of EAU as well as ocular cytokine production. An anti-inflammatory effect associated with the inhibition of T-cell proliferation and Th1 and Th17 cytokine production was observed. Increases in the Th2 response and Treg population were not observed with AICAR treatment. AICAR did significantly inhibit BMDC maturation by reducing co-stimulatory molecule expression.
CONCLUSIONS: AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cells. Impaired DC maturation may be an underlying mechanism for this anti-inflammatory effect observed with AICAR.
Authors:
Jun Suzuki; Takeru Yoshimura; Marina Simeonova; Kimio Takeuchi; Yusuke Murakami; Yuki Morizane; Joan W Miller; Lucia Sobrin; Demetrios G Vavvas
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2012-06-28
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  53     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-29     Completed Date:  2012-09-18     Revised Date:  2013-04-01    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4158-69     Citation Subset:  IM    
Affiliation:
Retina Service, Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
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MeSH Terms
Descriptor/Qualifier:
Aminoimidazole Carboxamide / administration & dosage,  analogs & derivatives*,  therapeutic use
Animals
Autoimmune Diseases / drug therapy*,  immunology,  metabolism
Blotting, Western
Cell Proliferation
Cytokines / metabolism
Disease Models, Animal
Female
Flow Cytometry
Hypoglycemic Agents / administration & dosage,  therapeutic use
Immunity, Cellular*
Injections, Intraperitoneal
Mice
Mice, Inbred C57BL
Ribonucleotides / administration & dosage*,  therapeutic use
T-Lymphocytes / immunology*
Treatment Outcome
Uvea / immunology,  metabolism,  pathology
Uveitis / drug therapy*,  immunology,  metabolism
Chemical
Reg. No./Substance:
0/Cytokines; 0/Hypoglycemic Agents; 0/Ribonucleotides; 360-97-4/Aminoimidazole Carboxamide; F0X88YW0YK/AICA ribonucleotide
Comments/Corrections

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