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NK1.1 Cells Downregulate Murine Endotoxin‐Induced Uveitis Following Intraocular Administration of Interleukin‐12
Author(s) -
Figueiredo F.,
Commodaro A. G.,
De Camargo M. M.,
Rizzo L. V.,
Belfort R.
Publication year - 2007
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2007.01988.x
Subject(s) - chemokine , microbiology and biotechnology , interferon gamma , antibody , immunology , chemistry , interleukin , biology , cytokine , inflammation
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.