title: Triptolide attenuates idiopathic pneumonia syndrome in a mouse bone marrow transplantation model by down-regulation of IL-17.
abstract: Idiopathic pneumonia syndrome (IPS) accounts for significant morbidity and mortality in patients following bone marrow transplantation (BMT). However, no effective therapy has been identified to reliably treat IPS. Previous studies using mouse BMT models suggest that the pathology of IPS in IFN-γ deficient host involves increased IL-17 levels along with recruitment of donor T cells into lung. Triptolide is a potent immunosuppressive compound isolated from an anti-inflammatory Chinese herbal medicine. Triptolide can significantly inhibit generation of IL-17 by T cells and mediate immunosuppressive effect on autoimmune disease. In the present study, we used a specific murine BMT model (IFN-γ deficient B6 to wildtype B6D2F1) to assess the protective effect of Triptolide on the development of IPS. We observed that IL-17 levels were significantly decreased in the lung after triptolide treatment compared with vehicle group. Furthermore, decreased number of Th17 cells in lung was found to be associated with amelioration of lung histological injury and pulmonary dysfunction. Additionally, neutralization of IL-17 also significantly reduced IPS pathology. Our study implied that triptolide could significantly inhibit donor T cell recruitment into lung, and thus prevent lung dysfunction after BMT usefully and effectively. Our study may shed some light on searching for proper strategies to prevent IL-17 mediated IPS and other Th17 cell-mediated immune pathologies.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Xu
authors.forename: Minjian
authors.initials: M
authors.lastname: Xiong
authors.forename: Yafei
authors.initials: Y
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Su
authors.forename: Ping
authors.initials: P
authors.lastname: Zou
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015415:Biomarkers; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010616:Phenanthrenes / Q000494:pharmacology*; D011014:Pneumonia / Q000188:drug therapy / Q000209:etiology*
chemical_list: D015415:Biomarkers; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D010616:Phenanthrenes; C001899:triptolide