Nasal IL-12p70 DNA prevents and treats intestinal allergic diarrhea.
OVA-induced allergic diarrhea occurs as a consequence of over-expression of Th1 inhibitory IL-12p40 monomers and homodimers in the large intestine, establishing a dominant Th2-type environment. In this study, we demonstrate that intranasally administered murine IL-12p70 naked DNA expression plasmids resulted in the synthesis of corresponding cytokine in the large intestinal CD11c(+) dendritic cells, leading to the inhibition of Ag-specific Th2-type response for the prevention of allergic diarrhea and the suppression of clinical symptoms including OVA-specific IgE Ab synthesis. The nasal IL-12p70 DNA treatment proved effective even after the establishment of allergic diarrhea. These results suggest that the mucosal administration of naked IL-12p70 DNA plasmid should be considered as a possible preventive and therapeutic treatment for Th2 cell-mediated food allergic diseases in the intestinal tract.
Hino
Ayako
A
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Japan.
Fukuyama
Satoshi
S
Kataoka
Kosuke
K
Kweon
Mi-Na
MN
Fujihashi
Kohtaro
K
Kiyono
Hiroshi
H
D000281:Administration, Intranasal; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003967:Diarrhea / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D007420:Intestine, Large / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D009305:Nasopharynx / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000633:toxicity; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D021122:Protein Subunits / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology* / Q000627:therapeutic use
D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D021122:Protein Subunits; D019444:Vaccines, DNA; D049452:Green Fluorescent Proteins; D018664:Interleukin-12; D010047:Ovalbumin