HMGB1 Accelerates Alveolar Epithelial Repair via an IL-1β- and αvβ6 Integrin-dependent Activation of TGF-β1
Open Access
- 16 May 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (5), e63907
- https://doi.org/10.1371/journal.pone.0063907
Abstract
High mobility group box 1 (HMGB1) protein is a danger-signaling molecule, known to activate an inflammatory response via TLR4 and RAGE. HMGB1 can be either actively secreted or passively released from damaged alveolar epithelial cells. Previous studies have shown that IL-1β, a critical mediator acute lung injury in humans that is activated by HMGB1, enhances alveolar epithelial repair, although the mechanisms are not fully understood. Herein, we tested the hypothesis that HMGB1 released by wounded alveolar epithelial cells would increase primary rat and human alveolar type II cell monolayer wound repair via an IL-1β-dependent activation of TGF-β1. HMGB1 induced in primary cultures of rat alveolar epithelial cells results in the release of IL-1β that caused the activation of TGF-β1 via a p38 MAPK-, RhoA- and αvβ6 integrin-dependent mechanism. Furthermore, active TGF-β1 accelerated the wound closure of primary rat epithelial cell monolayers via a PI3 kinase α-dependent mechanism. In conclusion, this study demonstrates that HMGB1 released by wounded epithelial cell monolayers, accelerates wound closure in the distal lung epithelium via the IL-1β-mediated αvβ6-dependent activation of TGF-β1, and thus could play an important role in the resolution of acute lung injury by promoting repair of the injured alveolar epithelium.Keywords
This publication has 55 references indexed in Scilit:
- HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4The Journal of Experimental Medicine, 2012
- The Milieu of Damaged Alveolar Epithelial Type 2 Cells Stimulates Alveolar Wound Repair by Endogenous and Exogenous ProgenitorsAmerican Journal of Respiratory Cell and Molecular Biology, 2011
- Vimentin is sufficient and required for wound repair and remodeling in alveolar epithelial cellsThe FASEB Journal, 2011
- HMGB1 induces human lung endothelial cell cytoskeletal rearrangement and barrier disruptionMicrovascular Research, 2010
- Exposure to Hydrogen Peroxide Induces Oxidation and Activation of AMP-activated Protein Kinase*Journal of Biological Chemistry, 2010
- Epithelial repair mechanisms in the lungAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2010
- S-Glutathionylation of the Rpn2 Regulatory Subunit Inhibits 26 S Proteasomal FunctionPublished by Elsevier BV ,2009
- Interleukin-1β Causes Acute Lung Injury via αvβ5 and αvβ6 Integrin–Dependent MechanismsCirculation Research, 2008
- Activation of Transforming Growth Factor-β by the Integrin αvβ8 Delays Epithelial Wound ClosureAmerican Journal of Respiratory Cell and Molecular Biology, 2006
- A Pharmacological Map of the PI3-K Family Defines a Role for p110α in Insulin SignalingCell, 2006