title: Green tea epigallo-catechin-galleate ameliorates the development of obliterative airway disease.
abstract: Lung transplantation has the worst outcome compared to all solid organ transplants due to chronic rejection known as obliterative bronchiolitis (OB). Pathogenesis of OB is a complex interplay of alloimmune-dependent and -independent factors, which leads to the development of inflammation, fibrosis, and airway obliteration that have been resistant to therapy. The alloimmune-independent inflammatory pathway has been the recent focus in the pathogenesis of rejection, suggesting that targeting this may offer therapeutic benefits. As a potent anti-inflammatory agent, epigallo-catechin-galleate (EGCG), a green tea catechin, has been very effective in ameliorating inflammation in a variety of diseases, providing the rationale for its use in this study in a murine heterotopic tracheal allograft model of OB. Mice treated with EGCG had reduced inflammation, with significantly less neutrophil and macrophage infiltration and significantly reduced fibrosis. On further investigation into the mechanisms, inflammatory cytokines keratinocyte (KC), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α), involved in neutrophil recruitment, were reduced in the EGCG-treated mice. In addition, monocyte chemokine monocyte chemoattractant protein-1 (MCP-1) was significantly reduced by EGCG treatment. Antifibrotic cytokine interferon-γ-inducible protein-10 (IP-10) was increased and profibrotic cytokine transforming growth factor-β (TGF-β) was reduced, further characterizing the antifibrotic effects of EGCG. These findings suggest that EGCG has great potential in ameliorating the development of obliterative airway disease.
authors.affiliation: Department of Medicine, Division of Respiratory Diseases, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Olin D
authors.initials: OD
authors.lastname: Liang
authors.forename: Bjoern E
authors.initials: BE
authors.lastname: Kleibrink
authors.forename: Katharina
authors.initials: K
authors.lastname: Schuette-Nuetgen
authors.forename: Umakanth U
authors.initials: UU
authors.lastname: Khatwa
authors.forename: Bechara
authors.initials: B
authors.lastname: Mfarrej
authors.forename: Meera
authors.initials: M
authors.lastname: Subramaniam
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines; D005355:Fibrosis / Q000517:prevention & control; D007249:Inflammation / Q000188:drug therapy; D016040:Lung Transplantation / Q000009:adverse effects; D051379:Mice; D020556:Neutrophil Infiltration; D013662:Tea
chemical_list: D016207:Cytokines; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate