Nishiyori Atsushi, Nagakura Yasunori, Ichikawa Katsuomi
Discovery Biology Research, Nagoya Laboratories, Pfizer Global Research and Development, Pfizer Inc., Taketoyo, Aichi, Japan.
Eur J Pharmacol. 2009 Aug 1;615(1-3):241-5. doi: 10.1016/j.ejphar.2009.05.002. Epub 2009 May 14.
T-cell receptor alpha chain (TCR.alpha)-deficient mice spontaneously develop colitis that resembles human ulcerative colitis; however, the incidence varies among individuals and takes place lately in the life. We have demonstrated that piroxicam induces colitis in non-colitic TCR.alpha-deficient mice, but not wild-type mice, within 14 days. The histological features and cytokine profiles were similar to those seen in spontaneous colitis in TCR.alpha-deficient mice. Dexamethasone prevented piroxicam-induced colitis concurrent with the suppression of interleukin (IL)-1beta, IL-17, tumor necrosis factor alpha and interferon gamma. This modified model of colitis could be useful for the evaluation of potential therapeutics for ulcerative colitis.
T细胞受体α链（TCRα）缺陷型小鼠会自发发展出类似于人类溃疡性结肠炎的结肠炎；然而，其发病率在个体间存在差异，且在生命后期才会出现。我们已经证明，吡罗昔康可在14天内诱导非结肠炎型TCRα缺陷型小鼠发生结肠炎，但对野生型小鼠无此作用。其组织学特征和细胞因子谱与TCRα缺陷型小鼠自发性结肠炎相似。地塞米松可预防吡罗昔康诱导的结肠炎，同时抑制白细胞介素（IL）-1β、IL-17、肿瘤坏死因子α和干扰素γ。这种改良的结肠炎模型可能有助于评估溃疡性结肠炎的潜在治疗方法。
