Identification of CpG oligodeoxynucleotide sequences that induce IFN-gamma production in canine peripheral blood mononuclear cells.
Oligodeoxynucleotides containing the cytosine-phosphate-guanine (CpG) motif (CpG-ODNs) have been shown to induce T(H)1 immune responses in animals. Since the sequences of CpG-ODNs that induce T(H)1 responses are considered to vary among animal species, it is necessary to identify effective CpG-ODNs in each animal. In order to identify the sequences of CpG-ODNs that induce T(H)1 responses in dogs, mRNA expression and protein production of IFN-gamma were examined in peripheral blood mononuclear cells (PBMCs) from healthy dogs treated with 11 kinds of synthetic CpG-ODNs. One of the 11 CpG-ODNs (No. 2 CpG-ODN, 5'-GGTGCATCGATGCAGGGGGG-3') was shown to significantly increase mRNA expression and protein production of IFN-gamma in canine PBMCs in a manner dependent on the sequence of the CpG motif. This CpG-ODN also enhanced the expression of IL-12 p40 mRNA in canine PBMCs, whereas expression of IL-12 p35, IL-18, and IL-4 mRNAs was not induced by this CpG-ODN. These results indicate that this CpG-ODN was able to produce IFN-gamma by induction of T(H)1-skewed immune response in dogs. CpG-ODNs may be useful for inducing prophylactic and therapeutic immunity against allergic diseases, viral infection, and tumors in dogs.
Kurata
Keigo
K
Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Iwata
Akira
A
Masuda
Kenichi
K
Sakaguchi
Masahiro
M
Ohno
Koichi
K
Tsujimoto
Hajime
H
D000818:Animals; D001483:Base Sequence; D015226:Dinucleoside Phosphates / Q000276:immunology*; D004285:Dogs / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism
D015226:Dinucleoside Phosphates; D007371:Interferon-gamma; D018664:Interleukin-12; D020382:Interleukin-18; D015847:Interleukin-4; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C015772:CpG dinucleotide