title: Blockade of interferon-gamma-inducible protein-10 attenuates chronic experimental colitis by blocking cellular trafficking and protecting intestinal epithelial cells.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan. kjsuzuki@med.niigata-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawauchi
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Palaniyandi
authors.forename: Punniyakoti T
authors.initials: PT
authors.lastname: Veeraveedu
authors.forename: Masato
authors.initials: M
authors.lastname: Fujii
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagiwa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Gi Dong
authors.initials: GD
authors.lastname: Han
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Okada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hosono
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Asakura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Shosaku
authors.initials: S
authors.lastname: Narumi
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000276:immunology; D002908:Chronic Disease; D003092:Colitis / Q000378:metabolism / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000517:prevention & control*; D021381:Protein Transport / Q000187:drug effects
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D019394:Ki-67 Antigen