NK1.1 cells downregulate murine endotoxin-induced uveitis following intraocular administration of interleukin-12.
To evaluate the role of IFN-gamma (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-gamma-deficient (GKO) mice were injected with 250 microg 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-gamma 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-gamma 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-gamma by NK1.1+ cells. IL-12-induced higher levels of IFN-gamma are also correlated with lower expression of the chemokine KC, resulting in diminished attraction of neutrophils to the inflammatory site.
Figueiredo
F
F
Walter Johnson High School AP Biology Program, Rockville, MD, USA.
Commodaro
A G
AG
de Camargo
M M
MM
Rizzo
L V
LV
Belfort
R
R
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000502:physiology; D015536:Down-Regulation / Q000276:immunology*; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000172:deficiency / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008845:Microinjections; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014605:Uveitis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*
D000950:Antigens, Ly; D000954:Antigens, Surface; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D055651:NK Cell Lectin-Like Receptor Subfamily B; D018664:Interleukin-12