Home
|
Inbox
|
Search
|
View Abstract
A Causative Role for Inflammatory Peroxidase Enzymes in Bleomycin-Induced Pulmonary Fibrosis
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A2215 - A Causative Role for Inflammatory Peroxidase Enzymes in Bleomycin-Induced Pulmonary Fibrosis
Author Block: C. DiFelice1, I. Zinonos1, M. O. DeNichilo2, A. Evdokiou1, V. Panagopoulos1; 1The University of Adelaide, Adelaide, Australia, 2The University of South Australia, Adelaide, Australia.
Rationale: Fibrotic lung disease, most notably idiopathic pulmonary fibrosis (IPF), is thought to result from aberrant wound-healing responses to repetitive lung injury. The release of inflammatory mediators such as myeloperoxidase (MPO) and eosinophil peroxidase (EPO) is a cardinal response to tissue injury, but whether they are mechanistically linked to pulmonary fibrosis is unknown. We have recently reported a role for MPO and EPO in the regulation of cutaneous wound healing by inducing dermal fibroblast collagen protein synthesis and migration. Here, we investigated whether MPO and EPO regulate pulmonary fibrosis both in vitro and in vivo. Methods: Human lung fibroblasts were pretreated with a small molecule inhibitor of peroxidase catalytic activity (5 µM) and the effects on MPO and EPO (both 6.25 µg/ml) induced type I collagen protein synthesis and migration were assessed by ELISA and 24-Multiwell Insert Systems (BD Biosciences). In vivo studies examined the effects of orally administered peroxidase inhibitor (100 mg/kg/day) on lung fibrosis in C57BL/6 mice endotracheally challenged with bleomycin (2.5 U/kg). Results: Pretreatment of human lung fibroblasts with the small molecule inhibitor of peroxidase catalytic activity markedly reduced MPO and EPO induced type I collagen protein synthesis and migration. In vivo, endotracheal administration of bleomycin resulted in increased expression of MPO and EPO in mouse lungs, localised to fibrotic regions. Mice treated with the peroxidase inhibitor for 7 days after endotracheal instillation of bleomycin had attenuation of lung fibrosis. Conclusion: Our findings support a role for MPO and EPO in bleomycin-induced pulmonary fibrosis and suggest that targeting these enzymes may represent a novel therapeutic strategy for IPF, which could have applicability to a wide range of fibrotic illnesses.
Author Block: C. DiFelice1, I. Zinonos1, M. O. DeNichilo2, A. Evdokiou1, V. Panagopoulos1; 1The University of Adelaide, Adelaide, Australia, 2The University of South Australia, Adelaide, Australia.
Rationale: Fibrotic lung disease, most notably idiopathic pulmonary fibrosis (IPF), is thought to result from aberrant wound-healing responses to repetitive lung injury. The release of inflammatory mediators such as myeloperoxidase (MPO) and eosinophil peroxidase (EPO) is a cardinal response to tissue injury, but whether they are mechanistically linked to pulmonary fibrosis is unknown. We have recently reported a role for MPO and EPO in the regulation of cutaneous wound healing by inducing dermal fibroblast collagen protein synthesis and migration. Here, we investigated whether MPO and EPO regulate pulmonary fibrosis both in vitro and in vivo. Methods: Human lung fibroblasts were pretreated with a small molecule inhibitor of peroxidase catalytic activity (5 µM) and the effects on MPO and EPO (both 6.25 µg/ml) induced type I collagen protein synthesis and migration were assessed by ELISA and 24-Multiwell Insert Systems (BD Biosciences). In vivo studies examined the effects of orally administered peroxidase inhibitor (100 mg/kg/day) on lung fibrosis in C57BL/6 mice endotracheally challenged with bleomycin (2.5 U/kg). Results: Pretreatment of human lung fibroblasts with the small molecule inhibitor of peroxidase catalytic activity markedly reduced MPO and EPO induced type I collagen protein synthesis and migration. In vivo, endotracheal administration of bleomycin resulted in increased expression of MPO and EPO in mouse lungs, localised to fibrotic regions. Mice treated with the peroxidase inhibitor for 7 days after endotracheal instillation of bleomycin had attenuation of lung fibrosis. Conclusion: Our findings support a role for MPO and EPO in bleomycin-induced pulmonary fibrosis and suggest that targeting these enzymes may represent a novel therapeutic strategy for IPF, which could have applicability to a wide range of fibrotic illnesses.
|
Home
|
Inbox
|
Search
|