title: Role of IP-10/CXCL10 in the progression of pancreatitis-like injury in mice after murine retroviral infection.
abstract: Exocrinopathy and pancreatitis-like injury were developed in C57BL/6 (B6) mice infected with LP-BM5 murine leukemia virus, which is known to induce murine acquired immunodeficiency syndrome (MAIDS). The role of chemokines, especially CXCL10/interferon (IFN)-gamma-inducible protein 10 (IP-10), a chemokine to attract CXCR3+ T helper 1-type CD4+ T cells, has not been investigated thoroughly in the pathogenesis of pancreatitis. B6 mice were inoculated intraperitoneally with LP-BM5 and then injected every week with either an antibody against IP-10 or a control antibody. Eight weeks after infection, we analyzed the effect of IP-10 neutralization. Anti-IP-10 antibody treatment did not change the generalized lymphadenopathy and hepatosplenomegaly of mice with MAIDS. The treatment significantly reduced the number of IP-10- and CXCR3-positive cells in the mesenteric lymph nodes (mLNs) but not the phenotypes and gross numbers of cells. In contrast, IP-10 neutralization reduced the number of mononuclear cells infiltrating into the pancreas. Anti-IP-10 antibody treatment did not change the numbers of IFN-gamma+ and IL10+ cells in the mLN but significantly reduced their numbers, especially IFN-gamma+ and IL-10+ CD4+ T cells and IFN-gamma+ Mac-1+ cells, in the pancreas. IP-10 neutralization ameliorated the pancreatic lesions of mice with MAIDS probably by blocking the cellular infiltration of CD4+ T cells and IFN-gamma+ Mac-1+ cells into the pancreas at least at 8 wk after infection, suggesting that IP-10 and these cells might play a key role in the development of chronic autoimmune pancreatitis.
authors.affiliation: Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawauchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Shiro
authors.initials: S
authors.lastname: Watanabe
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: Suresh S
authors.initials: SS
authors.lastname: Palaniyandi
authors.forename: Punniyakoti T
authors.initials: PT
authors.lastname: Veeraveedu
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Okada
authors.forename: Fujio
authors.initials: F
authors.lastname: Shimizu
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; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D007155:Immunologic Factors / Q000276:immunology*; D051379:Mice; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology*; D010195:Pancreatitis / Q000209:etiology* / Q000276:immunology*; D012192:Retroviridae Infections / Q000150:complications / Q000276:immunology
chemical_list: D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; D007155:Immunologic Factors