Document Detail

Controlling herpes simplex virus-induced ocular inflammatory lesions with the lipid-derived mediator resolvin E1.
MedLine Citation:
PMID:  21187448     Owner:  NLM     Status:  MEDLINE    
Stromal keratitis (SK) is a chronic immunopathological lesion of the eye caused by HSV-1 infection and a common cause of blindness in humans. The inflammatory lesions are primarily perpetuated by neutrophils with the active participation of CD4(+) T cells. Therefore, targeting these immune cell types represents a potentially valuable form of therapy to reduce the severity of disease. Resolvin E1 (RvE1), an endogenous lipid mediator, was shown to promote resolution in several inflammatory disease models. In the current report, we determined whether RvE1 administration begun at different times after ocular infection of mice with HSV could influence the severity of SK lesions. Treatment with RvE1 significantly reduced the extent of angiogenesis and SK lesions that occurred. RvE1-treated mice had fewer numbers of inflammatory cells that included Th1 and Th17 cells as well as neutrophils in the cornea. The mechanisms by which RvE1 acts appear to be multiple. These included reducing the influx of neutrophils and pathogenic CD4(+) T cells, increasing production of the anti-inflammatory cytokine IL-10, and inhibitory effects on the production of proinflammatory mediators and molecules, such as IL-6, IFN-γ, IL-17, KC, VEGF-A, MMP-2, and MMP-9, that are involved in corneal neovascularization and SK pathogenesis. These findings are, to our knowledge, the first to show that RvE1 treatment could represent a novel approach to control lesion severity in a virally induced immunopathological disease.
Naveen K Rajasagi; Pradeep B J Reddy; Amol Suryawanshi; Sachin Mulik; Per Gjorstrup; Barry T Rouse
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-27
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-20     Completed Date:  2011-03-07     Revised Date:  2014-11-11    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1735-46     Citation Subset:  AIM; IM    
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MeSH Terms
Administration, Topical
Angiogenesis Inhibitors / administration & dosage
Antiviral Agents / administration & dosage*
CD4-Positive T-Lymphocytes / drug effects,  immunology,  pathology
Cell Movement / drug effects,  immunology
Cornea / blood supply,  drug effects
Disease Models, Animal
Eicosapentaenoic Acid / administration & dosage,  analogs & derivatives*
Herpesvirus 1, Human / drug effects,  immunology*
Inflammation Mediators / administration & dosage*
Keratitis, Herpetic / immunology*,  prevention & control*,  virology
Mice, Inbred BALB C
Neutrophils / drug effects,  immunology,  pathology
Grant Support
Reg. No./Substance:
0/5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid; 0/Angiogenesis Inhibitors; 0/Antiviral Agents; 0/Inflammation Mediators; AAN7QOV9EA/Eicosapentaenoic Acid

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