Inability of IL-12 to down-regulate IgE synthesis due to defective production of IFN-gamma in atopic NC/Nga mice.
NC/Nga mice raised in nonsterile circumstances spontaneously suffer from atopic dermatitis-like skin lesions with IgE hyperproduction. We investigated effects of rIL-12 on the IgE production in NC/Nga mice. rIL-12 administration was successful to suppress the increase of IgE levels in BALB/c mice immunized with OVA and aluminum hydroxide, but failed to abrogate that in NC/Nga mice. Both in vivo and in vitro IFN-gamma production induced by rIL-12 was less in NC/Nga mice than in BALB/c mice. Addition of rIFN-gamma to rIL-4 and LPS completely abrogated IgE production by B cells of BALB/c mice, but was insufficient to suppress it by B cells of NC/Nga mice. In splenic cells pretreated with Con A, STAT4 was phosphorylated at the tyrosine residue by addition of rIL-12, which was more weakly inducible in NC/Nga mice than in BALB/c mice. Finally, we examined the preventive ability of rIL-12 on the clinical aspects of atopic dermatitis in NC/Nga mice. rIL-12 administration resulted in exacerbation of development of the skin lesions and IgE production in NC/Nga mice raised in nonsterile circumstances. These results suggest that defective production of IFN-gamma by T cells less sensitive to IL-12 and low responsiveness of B cells to IFN-gamma may contribute to IgE hyperproduction in NC/Nga mice, and that IL-12 may have no ability to improve the clinical aspects of NC/Nga mice.
Matsumoto
M
M
Laboratory of Clinical Immunology, Department of Veterinary Clinic, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
Itakura
A
A
Tanaka
A
A
Fujisawa
C
C
Matsuda
H
H
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology; D015536:Down-Regulation; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor; D050797:STAT4 Transcription Factor; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism; D000096743:Interferon gamma Receptor
D004268:DNA-Binding Proteins; D007073:Immunoglobulin E; D007371:Interferon-gamma; D018664:Interleukin-12; D008070:Lipopolysaccharides; D010047:Ovalbumin; D012333:RNA, Messenger; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050797:STAT4 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494080:Stat1 protein, mouse; C494091:Stat4 protein, mouse