The traditional herbal medicine saireito exerts its inhibitory effect on murine oxazolone-induced colitis via the induction of Th1-polarized immune responses in the mucosal immune system of the colon.
BACKGROUND
Ulcerative colitis is an intractable inflammatory colonic disease, and its etiology remains unclear. Saireito, a traditional herbal medicine, is widely used for treating ulcerative colitis in Japan. We analyzed the immunological characteristics of an oxazolone (OXZ)-induced colitis (OC) model and examined the effects of sareito on this model.


METHODS
OXZ was injected into the colon of BALB/c mice. Saireito was orally administered once a day for 3 consecutive days. Colitis was assessed by scoring the symptoms and macroscopic findings. The transcription patterns in the middle colon and spleen were analyzed with global transcriptome analysis and real-time polymerase chain reaction (PCR).


RESULTS
The above-mentioned scores were increased in the OC mice. The transcription levels of Th2 cytokines were significantly upregulated in the spleen and middle colon of the OC mice, whereas those of the Th1 cytokine interferon (IFN)-gamma decreased in the spleen and increased in the middle colon. Saireito significantly ameliorated OC. In the middle colon of the saireito-treated mice, enhanced expression of Th2 cytokine mRNAs was markedly downregulated, while that of IFN-gamma mRNA was further upregulated. In contrast, in the spleen, saireito had no effect on the transcription of either type of cytokine. After global transcriptome analysis, real-time PCR analysis revealed that saireito greatly downregulated the enhanced expression of the suppressor of cytokine signaling (SOCS)-3 mRNA in the middle colon of OC mice.


CONCLUSIONS
Saireito exhibits inhibitory effects on OC by the induction of Th1-polarized immune responses in the mucosal immune system of the colon.
Watanabe
Tetsuo
T
Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan.
Yamamoto
Takeshi
T
Yoshida
Minako
M
Fujiwara
Kanae
K
Kageyama-Yahara
Natsuko
N
Kuramoto
Hirofumi
H
Shimada
Yutaka
Y
Kadowaki
Makoto
M
D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010081:Oxazolone / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D004365:Drugs, Chinese Herbal; D015848:Interleukin-5; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C080903:sairei-to; D016753:Interleukin-10; D010081:Oxazolone; D015847:Interleukin-4; D007371:Interferon-gamma