title: Lipoxin A4promotes lung epithelial repair whilst inhibiting fibroblast proliferation.
abstract: Therapy that promotes epithelial repair whilst protecting against fibroproliferation is critical for restoring lung function in acute and chronic respiratory diseases. Primary human alveolar type II cells were used to model the effects of lipoxin A4in vitroupon wound repair, proliferation, apoptosis and transdifferention. Effects of lipoxin A4upon primary human lung fibroblast proliferation, collagen production, and myofibroblast differentiation were also assessed. Lipoxin A4promoted type II cell wound repair and proliferation, blocked the negative effects of soluble Fas ligand/tumour necrosis factor α upon cell proliferation, viability and apoptosis, and augmented the epithelial cell proliferative response to bronchoaveolar lavage fluid (BALF) from acute respiratory distress syndrome (ARDS). In contrast, Lipoxin A4reduced fibroblast proliferation, collagen production and myofibroblast differentiation induced by transforming growth factor β and BALF from ARDS. The effects of Lipoxin A4were phosphatidylinositol 3'-kinase dependent and mediatedviathe lipoxin A4receptor. Lipoxin A4appears to promote alveolar epithelial repair by stimulating epitheial cell wound repair, proliferation, reducing apoptosis and promoting trans-differentiation of alveolar type II cells into type I cells. Lipoxin A4reduces fibroblast proliferation, collagen production and myofibroblast differentiation. These data suggest that targeting lipoxin actions may be a therapeutic strategy for treating the resolution phase of ARDS.
authors.affiliation: Dept of Anaesthesia and Critical Care, Second Affiliated Hospital of Wenzhou Medical University, Zhejiang , China; Centre for Translational Inflammation and Fibrosis Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; Both authors contributed equally.
authors.forename: Shengxing
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; Both authors contributed equally.
authors.forename: Vijay K
authors.identifier: 0000-0002-9402-7516
authors.initials: VK
authors.lastname: D'Souza
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
authors.forename: Domokos
authors.identifier: 0000-0003-2301-3704
authors.initials: D
authors.lastname: Bartis
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
authors.forename: Rachel C A
authors.initials: RC
authors.lastname: Dancer
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
authors.forename: Dhruv
authors.initials: D
authors.lastname: Parekh
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
authors.forename: Babu
authors.initials: B
authors.lastname: Naidu
authors.affiliation: Dept of Anaesthesia and Critical Care, Second Affiliated Hospital of Wenzhou Medical University, Zhejiang , China; Centre for Translational Inflammation and Fibrosis Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
authors.forename: Fang
authors.initials: F
authors.lastname: Gao-Smith
authors.affiliation: Dept of Anaesthesia and Critical Care, Second Affiliated Hospital of Wenzhou Medical University, Zhejiang , China; Centre for Translational Inflammation and Fibrosis Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Dept of Anaesthesia and Critical Care, Second Affiliated Hospital of Wenzhou Medical University, Zhejiang , China.
authors.forename: Shengwei
authors.initials: S
authors.lastname: Jin
authors.affiliation: Dept of Anaesthesia and Critical Care, Second Affiliated Hospital of Wenzhou Medical University, Zhejiang , China.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Lian
authors.affiliation: Centre for Translational Inflammation and Fibrosis Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Thickett