title: Long-term exposure of chemokine CXCL10 causes bronchiolitis-like inflammation.
abstract: Chemokines and chemokine receptors have been implicated in the pathogenesis of bronchiolitis. CXCR3 ligands (CXCL10, CXCL9, and CXCL11) were elevated in patients with bronchiolitis obliterans syndrome (BOS) and chronic allorejection. Studies also suggested that blockage of CXCR3 or its ligands changed the outcome of T-cell recruitment and airway obliteration. We wanted to determine the role of the chemokine CXCL10 in the pathogenesis of bronchiolitis and BOS. In this study, we found that CXCL10 mRNA levels were significantly increased in patients with BOS. We generated transgenic mice expressing a mouse CXCL10 cDNA under control of the rat CC10 promoter. Six-month-old CC10-CXCL10 transgenic mice developed bronchiolitis characterized by airway epithelial hyperplasia and developed peribronchiolar and perivascular lymphocyte infiltration. The airway hyperplasia and T-cell inflammation were dependent on the presence of CXCR3. Therefore, long-term exposure of the chemokine CXCL10 in the lung causes bronchiolitis-like inflammation in mice.
authors.affiliation: Division of Pulmonary, Duke University School of Medicine, 106 Research Drive, Durham, NC 27710, USA.
authors.forename: Dianhua
authors.initials: D
authors.lastname: Jiang
authors.forename: Jiurong
authors.initials: J
authors.lastname: Liang
authors.forename: Rishu
authors.initials: R
authors.lastname: Guo
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
authors.forename: Francine L
authors.initials: FL
authors.lastname: Kelly
authors.forename: Tereza
authors.initials: T
authors.lastname: Martinu
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Alysia K
authors.initials: AK
authors.lastname: Lovgren
authors.forename: Jessica
authors.initials: J
authors.lastname: Chia
authors.forename: Ningshan
authors.initials: N
authors.lastname: Liu
authors.forename: Yoosun
authors.initials: Y
authors.lastname: Jung
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
mesh_terms: D000818:Animals; D001483:Base Sequence; D001988:Bronchiolitis / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid; D054357:Chemokine CXCL10 / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D017931:DNA Primers; D012333:RNA, Messenger