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Suppressor of Cytokine Signaling 1 (SOCS1) Mitigates Anterior Uveitis and Confers Protection Against Ocular HSV-1 Infection.
- Source :
-
Inflammation . Apr2015, Vol. 38 Issue 2, p555-565. 11p. - Publication Year :
- 2015
-
Abstract
- Immunological responses to pathogens are stringently regulated in the eye to prevent excessive inflammation that damage ocular tissues and compromise vision. Suppressors of cytokine signaling (SOCS) regulate intensity/duration of inflammatory responses. We have used SOCS1-deficient mice and retina-specific SOCS1 transgenic rats to investigate roles of SOCS1 in ocular herpes simplex virus (HSV-1) infection and non-infectious uveitis. We also genetically engineered cell-penetrating SOCS proteins (membrane-translocating sequence (MTS)-SOCS1, MTS-SOCS3) and examined whether they can be used to inhibit inflammatory cytokines. Overexpression of SOCS1 in transgenic rat eyes attenuated ocular HSV-1 infection while SOCS1-deficient mice developed severe non-infectious anterior uveitis, suggesting that SOCS1 may contribute to mechanism of ocular immune privilege by regulating trafficking of inflammatory cells into ocular tissues. Furthermore, MTS-SOCS1 inhibited IFN-γ-induced signal transducers and activators of transcription 1 (STAT1) activation by macrophages while MTS-SOCS3 suppressed expansion of pathogenic Th17 cells that mediate uveitis, indicating that MTS-SOCS proteins maybe used to treat ocular inflammatory diseases of infectious or autoimmune etiology. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03603997
- Volume :
- 38
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 101226387
- Full Text :
- https://doi.org/10.1007/s10753-014-9962-6