{"title":"在活性葡聚糖硫酸钠诱导的结肠炎期间,可诱导口服耐受性。","authors":"Satoshi Ino, Chikara Kohda, Kosuke Takeshima, Hiroki Ishikawa, Tomoko Norose, Toshiko Yamochi, Masafumi Takimoto, Hiroshi Takahashi, Kazuo Tanaka","doi":"10.4292/wjgpt.v7.i2.242","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>To investigate whether oral tolerance is inducible during the active phase of dextran sulfate sodium (DSS)-induced colitis.</p><p><strong>Methods: </strong>Colitis was induced in 6- to 8-wk-old female BALB/c mice by the administration of 2% DSS. To induce oral tolerance, mice that received water with DSS [DSS (+)] and mice that received autoclaved water [DSS (-)] were intragastrically (i.g.) administered ovalbumin (OVA) as a tolerogen before systemic challenge with OVA. Following this, serum levels of OVA-specific IgE antibodies were measured. In mice with active colitis, CD4(+)CD25(+)Foxp3(+) cell and B10 cell frequencies were evaluated using flow cytometry. Cytokine mRNA expression profiles were evaluated by reverse transcription real-time polymerase chain reaction.</p><p><strong>Results: </strong>Regardless of the presence of DSS colitis, OVA-specific immunoglobulin E concentrations were significantly reduced in mice that were i.g. administered OVA compared to mice that were i.g. administered PBS [DSS (+): 4.4 (4.2-9.5) ng/mL vs 83.9 (66.1-123.2) ng/mL, P < 0.01; DSS (-): 27.7 (0.1-54.5) ng/mL vs 116.5 (80.6-213.6) ng/mL, P < 0.01]. These results demonstrated that oral tolerance was induced in both the presence and absence of colitis. In the spleen and mesenteric lymph nodes (MLN), the frequencies of CD4(+)CD25(+)Foxp3(+) cells and B10 cells, both of which are associated with oral tolerance, did not significantly change. In the spleen, interferon-γ mRNA expression significantly decreased in mice with colitis [DSS (+): 0.42 (0.31-0.53) vs DSS (-): 1.00 (0.84-1.39), P < 0.01]. The expression levels of other cytokines did not significantly change.</p><p><strong>Conclusion: </strong>Oral tolerance is inducible during active DSS colitis. The stability of regulatory cell populations in the spleen and MLN in colitis might correlate with these results.</p>","PeriodicalId":23755,"journal":{"name":"World Journal of Gastrointestinal Pharmacology and Therapeutics","volume":"7 2","pages":"242-53"},"PeriodicalIF":0.0000,"publicationDate":"2016-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848247/pdf/WJGPT-7-242.pdf","citationCount":"5","resultStr":"{\"title\":\"Oral tolerance is inducible during active dextran sulfate sodium-induced colitis.\",\"authors\":\"Satoshi Ino, Chikara Kohda, Kosuke Takeshima, Hiroki Ishikawa, Tomoko Norose, Toshiko Yamochi, Masafumi Takimoto, Hiroshi Takahashi, Kazuo Tanaka\",\"doi\":\"10.4292/wjgpt.v7.i2.242\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>To investigate whether oral tolerance is inducible during the active phase of dextran sulfate sodium (DSS)-induced colitis.</p><p><strong>Methods: </strong>Colitis was induced in 6- to 8-wk-old female BALB/c mice by the administration of 2% DSS. To induce oral tolerance, mice that received water with DSS [DSS (+)] and mice that received autoclaved water [DSS (-)] were intragastrically (i.g.) administered ovalbumin (OVA) as a tolerogen before systemic challenge with OVA. Following this, serum levels of OVA-specific IgE antibodies were measured. In mice with active colitis, CD4(+)CD25(+)Foxp3(+) cell and B10 cell frequencies were evaluated using flow cytometry. Cytokine mRNA expression profiles were evaluated by reverse transcription real-time polymerase chain reaction.</p><p><strong>Results: </strong>Regardless of the presence of DSS colitis, OVA-specific immunoglobulin E concentrations were significantly reduced in mice that were i.g. administered OVA compared to mice that were i.g. administered PBS [DSS (+): 4.4 (4.2-9.5) ng/mL vs 83.9 (66.1-123.2) ng/mL, P < 0.01; DSS (-): 27.7 (0.1-54.5) ng/mL vs 116.5 (80.6-213.6) ng/mL, P < 0.01]. These results demonstrated that oral tolerance was induced in both the presence and absence of colitis. In the spleen and mesenteric lymph nodes (MLN), the frequencies of CD4(+)CD25(+)Foxp3(+) cells and B10 cells, both of which are associated with oral tolerance, did not significantly change. In the spleen, interferon-γ mRNA expression significantly decreased in mice with colitis [DSS (+): 0.42 (0.31-0.53) vs DSS (-): 1.00 (0.84-1.39), P < 0.01]. The expression levels of other cytokines did not significantly change.</p><p><strong>Conclusion: </strong>Oral tolerance is inducible during active DSS colitis. The stability of regulatory cell populations in the spleen and MLN in colitis might correlate with these results.</p>\",\"PeriodicalId\":23755,\"journal\":{\"name\":\"World Journal of Gastrointestinal Pharmacology and Therapeutics\",\"volume\":\"7 2\",\"pages\":\"242-53\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2016-05-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848247/pdf/WJGPT-7-242.pdf\",\"citationCount\":\"5\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Gastrointestinal Pharmacology and Therapeutics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4292/wjgpt.v7.i2.242\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Gastrointestinal Pharmacology and Therapeutics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4292/wjgpt.v7.i2.242","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 5
摘要
目的:探讨葡聚糖硫酸钠(DSS)诱导结肠炎活性期是否可诱导口服耐受。方法:用2% DSS诱导6 ~ 8周龄BALB/c雌性小鼠结肠炎。为了诱导口服耐受,小鼠接受含有DSS(+)的水[DSS(-)]和小鼠接受高压灭菌水[DSS(-)],在用OVA进行全身攻击之前,腹腔注射卵清蛋白(OVA)作为耐受原。随后,测定ova特异性IgE抗体的血清水平。在活动性结肠炎小鼠中,采用流式细胞术检测CD4(+)、CD25(+)、Foxp3(+)细胞和B10细胞频率。逆转录实时聚合酶链反应检测细胞因子mRNA表达谱。结果:无论是否存在DSS结肠炎,与ig PBS小鼠相比,ig OVA小鼠的OVA特异性免疫球蛋白E浓度显著降低[DSS (+): 4.4 (4.2-9.5) ng/mL vs 83.9 (66.1-123.2) ng/mL, P < 0.01;DSS (-): 27.7 (0.1 - -54.5) ng / mL vs 116.5 ng / mL (80.6 - -213.6), P < 0.01)。这些结果表明,在存在和不存在结肠炎的情况下,口服耐受都是诱导的。在脾脏和肠系膜淋巴结(MLN)中,CD4(+)CD25(+)Foxp3(+)细胞和B10细胞的频率均与口服耐受性相关,但无明显变化。结肠炎小鼠脾脏中干扰素-γ mRNA表达显著降低[DSS (+): 0.42 (0.31-0.53) vs DSS (-): 1.00 (0.84-1.39), P < 0.01]。其他细胞因子的表达水平无明显变化。结论:活动性DSS结肠炎可诱导口服耐受。结肠炎患者脾脏和MLN中调节细胞群的稳定性可能与这些结果有关。
Oral tolerance is inducible during active dextran sulfate sodium-induced colitis.
Aim: To investigate whether oral tolerance is inducible during the active phase of dextran sulfate sodium (DSS)-induced colitis.
Methods: Colitis was induced in 6- to 8-wk-old female BALB/c mice by the administration of 2% DSS. To induce oral tolerance, mice that received water with DSS [DSS (+)] and mice that received autoclaved water [DSS (-)] were intragastrically (i.g.) administered ovalbumin (OVA) as a tolerogen before systemic challenge with OVA. Following this, serum levels of OVA-specific IgE antibodies were measured. In mice with active colitis, CD4(+)CD25(+)Foxp3(+) cell and B10 cell frequencies were evaluated using flow cytometry. Cytokine mRNA expression profiles were evaluated by reverse transcription real-time polymerase chain reaction.
Results: Regardless of the presence of DSS colitis, OVA-specific immunoglobulin E concentrations were significantly reduced in mice that were i.g. administered OVA compared to mice that were i.g. administered PBS [DSS (+): 4.4 (4.2-9.5) ng/mL vs 83.9 (66.1-123.2) ng/mL, P < 0.01; DSS (-): 27.7 (0.1-54.5) ng/mL vs 116.5 (80.6-213.6) ng/mL, P < 0.01]. These results demonstrated that oral tolerance was induced in both the presence and absence of colitis. In the spleen and mesenteric lymph nodes (MLN), the frequencies of CD4(+)CD25(+)Foxp3(+) cells and B10 cells, both of which are associated with oral tolerance, did not significantly change. In the spleen, interferon-γ mRNA expression significantly decreased in mice with colitis [DSS (+): 0.42 (0.31-0.53) vs DSS (-): 1.00 (0.84-1.39), P < 0.01]. The expression levels of other cytokines did not significantly change.
Conclusion: Oral tolerance is inducible during active DSS colitis. The stability of regulatory cell populations in the spleen and MLN in colitis might correlate with these results.