HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hooks, J. J. Articles by Detrick, B. PubMed PubMed Citation Articles by Hooks, J. J. Articles by Detrick, B.

IFN-β Provides Immuno-Protection in the Retina by Inhibiting ICAM-1 and CXCL9 in Retinal Pigment Epithelial Cells¹

John J. Hooks^2,*, Chandrasekharam N. Nagineni^*, Laura C. Hooper^*, Kozaburo Hayashi^* and Barbara Detrick

^* Immunology and Virology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287

The retinal pigment epithelial (RPE) cell is a potent regulatory cell that facilitates normal physiologic processes and plays a critical role in a variety of retinal diseases. We evaluated IFN-β production in human RPE cells through TLR signaling and investigated the effects of IFN-β on RPE cells. RPE cells treated with poly(I:C) or infected with an RNA virus produce IFN-β. Kinetic studies revealed that IFN-β levels continue to increase over a 48-h period and this was associated with the up-regulation of IRF-7 gene expression, a known positive feedback molecule for IFN-β production. Microarray analysis revealed that in IFN-β treated cells, 480 genes of 22,283 genes were up or down-regulated by >2-fold. We hypothesize that IFN-β induction during TLR signaling in the retina is an immunosuppressive factor produced to limit immunopathologic damage. Cytokine activation of RPE cells results in the production of the chemokines, CXCL9 and CXCL10, and the adhesion molecule, ICAM-1. Pretreatment of RPE cells with IFN-β resulted in inhibition of ICAM-1 production and elimination of CXCL9 production. This treatment did not alter CXCL10 production. Anti-IFN-β Ab blocked the inhibitory action of IFN-β. Real time PCR analysis revealed that IFN-β treatment inhibited gene expression of sICAM-1 and CXCL9. The results indicate a critical role for RPE cell derived IFN-β in the down-regulation of CXCL9 and ICAM-1 expression in the retina and suggest that the inhibition of CXCL9 is an immuno-suppressive mechanism that protects the retina from excessive inflammation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Intramural Research program of the National Eye Institute, National Institutes of Health.

² Address correspondence and reprint requests to Dr. John J. Hooks, National Eye Institute, National Institutes of Health, Building 10, Room 10N248, Bethesda, MD 20892. E-mail address: hooksj{at}nei.nih.gov

³ Abbreviations used in this paper: RPE, retinal pigment epithelium; VSV, Vesicular stomatitis virus; SFM, serum free medium; EIA, enzyme immunoassay; IRF, IFN regulatory factors; MS, multiple sclerosis.