Suzuki Kenji, Kawauchi Yusuke, Palaniyandi Suresh S, Veeraveedu Punniyakoti T, Fujii Masato, Yamagiwa Satoshi, Yoneyama Hiroyuki, Han Gi Dong, Kawachi Hiroshi, Okada Yoshiaki, Ajioka Yoichi, Watanabe Kenichi, Hosono Masamichi, Asakura Hitoshi, Aoyagi Yutaka, Narumi Shosaku
Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan.
Pathol Int. 2007 Jul;57(7):413-20. doi: 10.1111/j.1440-1827.2007.02117.x.
The role of chemokines, especially CXCL10/interferon-gamma-inducible protein 10 kDa (IP-10), a chemokine to attract CXCR3(+) T-helper 1-type CD4(+) T cells, is largely unknown in the pathophysiology of inflammatory bowel disease; ulcerative colitis and Crohn's disease. The authors have earlier shown that IP-10 neutralization protected mice from acute colitis by protecting crypt epithelial cells of the colon. To investigate the therapeutic effect of neutralization of IP-10 on chronic colitis, an anti-IP-10 antibody was injected into mice with newly established murine AIDS (MAIDS) colitis. Anti-IP-10 antibody treatment reduced the number of colon infiltrating cells when compared to those mice given a control antibody. The treatment made the length of the crypt of the colon greater than control antibody. The number of Ki67(+) proliferating epithelial cells was increased by the anti-IP-10 antibody treatment. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)(+) apoptotic cells were observed in the epithelial cells of the luminal tops of crypts in control MAIDS colitis, whereas TUNEL(+) apoptotic epithelial cells were rarely observed with anti-IP-10 antibody treatment. In conclusion, blockade of IP-10 attenuated MAIDS colitis through blocking cellular trafficking and protecting intestinal epithelial cells, suggesting that IP-10 plays a key role in the development of inflammatory bowel disease as well as in chronic experimental colitis.
趋化因子的作用，尤其是CXCL10/γ干扰素诱导蛋白10千道尔顿（IP-10），一种吸引CXCR3(+)辅助性T细胞1型CD4(+)T细胞的趋化因子，在炎症性肠病（溃疡性结肠炎和克罗恩病）的病理生理学中很大程度上尚不清楚。作者早些时候表明，IP-10中和通过保护结肠隐窝上皮细胞使小鼠免受急性结肠炎的侵害。为了研究IP-10中和对慢性结肠炎的治疗效果，将抗IP-10抗体注射到新建立的鼠类获得性免疫缺陷综合征（MAIDS）结肠炎小鼠体内。与给予对照抗体的小鼠相比，抗IP-10抗体治疗减少了结肠浸润细胞的数量。该治疗使结肠隐窝的长度大于对照抗体组。抗IP-10抗体治疗增加了Ki67(+)增殖上皮细胞的数量。在对照MAIDS结肠炎小鼠的隐窝腔顶部上皮细胞中观察到末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）(+)凋亡细胞，而抗IP-10抗体治疗很少观察到TUNEL(+)凋亡上皮细胞。总之，IP-10的阻断通过阻止细胞迁移和保护肠道上皮细胞减轻了MAIDS结肠炎，这表明IP-10在炎症性肠病的发展以及慢性实验性结肠炎中起关键作用。
