Rectal administration of tranilast ameliorated acute colitis in mice through increased expression of heme oxygenase‐1
Rectal administration of tranilast ameliorated acute colitis in mice through increased expression of heme oxygenase‐1
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DOI：
10.1111/j.1440-1827.2009.02490.x
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发表时间：
2010-02
影响因子：
2.2
通讯作者：
Xiaomei Sun;Kenji Suzuki;M. Nagata;Yusuke Kawauchi;M. Yano;S. Ohkoshi;Y. Matsuda;H. Kawachi;Kenichi Watanabe;H. Asakura;Y. Aoyagi
中科院分区：
文献类型：
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作者：
Xiaomei Sun;Kenji Suzuki;M. Nagata;Yusuke Kawauchi;M. Yano;S. Ohkoshi;Y. Matsuda;H. Kawachi;Kenichi Watanabe;H. Asakura;Y. Aoyagi
肥大细胞在炎症性肠病（IBD）的病理生理学中起关键作用。曲尼司特是一种肥大细胞稳定剂，在日本已被经验性地用于IBD，但其在IBD治疗中的确切作用在很大程度上是未知的。为了研究曲尼司特治疗IBD的作用，将曲尼司特直肠内给予患有葡聚糖硫酸钠（DSS）诱导的结肠炎的小鼠。曲尼司特改善DSS结肠炎的临床和病理学，表现为结肠肥大细胞数量减少和脱粒。在DSS结肠炎小鼠的结肠中，肿瘤坏死因子-α、干扰素-γ和白细胞介素（IL）-6的mRNA表达增加，而IL-10的mRNA表达减少。相反，曲尼司特显著降低促炎细胞因子的mRNA表达，并增加抗炎细胞因子的mRNA表达。此外，曲尼司特增加结肠上皮细胞以及DSS结肠炎的结肠浸润细胞上的血红素加氧酶（HO）-1表达。总之，曲尼司特通过调节肥大细胞脱颗粒、减少炎性细胞因子和增加抗炎性细胞因子来改善DSS结肠炎。曲尼司特可能部分通过增强结肠中HO-1的表达来发挥这些作用，这表明曲尼司特是IBD的潜在辅助治疗方法。
Mast cells play a key role in the pathophysiology of inflammatory bowel disease (IBD). Tranilast, a mast cell stabilizer, has been empirically used for IBD in Japan, but its precise role in the treatment of IBD is largely unknown. To investigate the role of tranilast for the treatment of IBD, tranilast was administered intrarectally to mice with dextran sulfate sodium (DSS)‐induced colitis. Tranilast ameliorated DSS colitis clinically and pathologically, as demonstrated by decreased number and degranulation of mast cells in the colon. mRNA expression was increased for tumor necrosis factor‐α, interferon‐γ and interleukin (IL)‐6, and decreased for IL‐10 in the colon of DSS colitis mice. In contrast, tranilast markedly decreased expression of mRNAs for the pro‐inflammatory cytokines, and increased that of the anti‐inflammatory cytokines. Moreover, tranilast increased heme oxygenase (HO)‐1 expression on colonic epithelial cells as well as on colon‐infiltrating cells of DSS colitis. In conclusion, tranilast ameliorated DSS colitis by regulating mast cell degranulation, decreasing inflammatory cytokines and increasing anti‐inflammatory cytokines. Tranilast might exert these effects partly through enhanced HO‐1 expression in the colon, suggesting a potential adjunctive therapy for IBD.