NK1.1 Cells Downregulate Murine Endotoxin-Induced Uveitis Following Intraocular Administration of Interleukin-12

To evaluate the role of IFN-γ (interferon gamma) in IL-12- (interleukin-12)-induced inhibition of the inflammatory response in the eye during endotoxin-induced uveitis (EIU). C57BL/6 wild type mice and IFN-γ-deficient (GKO) mice were injected with 250 μg of Salmonella typhymurium endotoxin as a mode...

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Bibliographic Details
Published in:Scandinavian journal of immunology 2007-08, Vol.66 (2-3), p.329-334
Main Authors: Figueiredo, F, Commodaro, A.G, de Camargo, M.M, Rizzo, L.V, Belfort, R. Jr
Format: Article
Language:English
Subjects:
Animals
Anterior Chamber - immunology
Antigens, Ly
Antigens, Surface - biosynthesis
Antigens, Surface - physiology
Down-Regulation - immunology
Immunophenotyping
Interleukin-12 - administration & dosage
Interleukin-12 - therapeutic use
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Lectins, C-Type - biosynthesis
Lectins, C-Type - deficiency
Lectins, C-Type - physiology
Lipopolysaccharides - administration & dosage
Lipopolysaccharides - antagonists & inhibitors
Lymphocyte Depletion
Mice
Mice, Inbred C57BL
Mice, Knockout
Microinjections
NK Cell Lectin-Like Receptor Subfamily B
Salmonella
Uveitis - immunology
Uveitis - metabolism
Uveitis - therapy
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Summary:To evaluate the role of IFN-γ (interferon gamma) in IL-12- (interleukin-12)-induced inhibition of the inflammatory response in the eye during endotoxin-induced uveitis (EIU). C57BL/6 wild type mice and IFN-γ-deficient (GKO) mice were injected with 250 μg of Salmonella typhymurium endotoxin as a model for EIU. Animals were then injected intraocularly with 100 ng of rIL-12 or the equivalent volume of Phosphate-buffer saline (PBS). Histopathologic grading of disease was performed 12, 36 and 72 h after endotoxin injection. Chemokine mRNA expression in the eye was evaluated by reverse transcriptase-polymerase chain reaction. Depletion of NK1.1+ cells in vivo was performed using a PK136 antibody. Depletion of IFN-γ was performed using the R4-6A2 antibody. C57BL/6 mice treated with rIL-12 intraocularly were protected from the development of EIU. Neutralization of IFN-γ with a monoclonal antibody abrogated such protection. The IL-12 protective effects were lost in NK1.1-depleted mice. Intraocular IL-12 decreased the expression of keratinocyte-derived chemokines (KC) gene but had no effect on macrophage inflammatory protein (MIP-2) gene. The protective effect of IL-12 during EIU occurs through production of IFN-γ by NK1.1+ cells. IL-12-induced higher levels of IFN-γ are also correlated with lower expression of the chemokine KC, resulting in diminished attraction of neutrophils to the inflammatory site.
ISSN:0300-9475
1365-3083
DOI:10.1111/j.1365-3083.2007.01988.x