PG490-88, a derivative of triptolide, attenuates obliterative airway disease in a mouse heterotopic tracheal allograft model.
The current treatment of obliterative bronchiolitis in lung transplant recipients is sub-optimal. Triptolide is a novel immunosuppressant that has a mechanism of action distinct from currently available immunosuppressants, including induction of T-cell apoptosis, blockade of fibroblast proliferation/maturation and inhibition of transforming growth factor-beta (TGF-beta) mRNA production. We hypothesized that triptolide may be helpful in blocking obliterative airway disease in lung transplant recipients. We investigated the effect of PG490-88, a water-soluble derivative of triptolide, in a mouse heterotopic tracheal allograft model of obliterative airway disease. We show that PG490-88 attenuates airway obliteration in this model and inhibits accumulation of inflammatory cells, and therefore may have preventive or therapeutic benefits for patients with obliterative airway disease (OAD) following lung transplantation.
Leonard
Colm T
CT
Division of Pulmonary and Critical Care Medicine, Department of Histopathology, Stanford University Medical Center, Stanford, California, USA. colm.leonard@yahoo.com
Soccal
Paola M
PM
Berry
Gerald J
GJ
Doyle
Ramona L
RL
Theodore
James
J
Duncan
Steven R
SR
Rosen
Glenn D
GD
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D006084:Graft Rejection; D006085:Graft Survival; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012016:Reference Values; D012680:Sensitivity and Specificity; D014132:Trachea / Q000473:pathology* / Q000637:transplantation*; D016042:Transplantation, Heterotopic; D016896:Treatment Outcome
D004224:Diterpenes; C417603:omtriptolide