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Blockade of interferon‐γ‐inducible protein‐10 attenuates chronic experimental colitis by blocking cellular trafficking and protecting intestinal epithelial cells
Author(s) -
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
Publication year - 2007
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2007.02117.x
Subject(s) - colitis , cxcl10 , tunel assay , antibody , inflammatory bowel disease , immunology , ulcerative colitis , chemokine , blocking antibody , crypt , cxcr3 , medicine , cancer research , biology , inflammation , immunohistochemistry , pathology , disease , chemokine receptor
The role of chemokines, especially CXCL10/interferon‐γ‐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.