HMGB1 Accelerates Alveolar Epithelial Repair via an IL-1β- and αvβ6 Integrin-dependent Activation of TGF-β1

Jean François Pittet, Hidefumi Koh, Xiaohui Fang, Karen Iles, Sarah Christiaans, Naseem Anjun, Brant M. Wagener, Dae Won Park, Jaroslaw W. Zmijewski, Michael A. Matthay, Jérémie Roux

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Article numbere63907
JournalPLoS One
Volume8
Issue number5
DOIs
Publication statusPublished - 2013 May 16

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Alveolar Epithelial Cells
integrins
interleukin-1
Interleukin-1
Integrins
epithelial cells
Repair
animal injuries
Chemical activation
Acute Lung Injury
Rats
Monolayers
lungs
Wounds and Injuries
Epithelium
Epithelial Cells
HMGB1 Protein
rats
epithelium
p38 Mitogen-Activated Protein Kinases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pittet, J. F., Koh, H., Fang, X., Iles, K., Christiaans, S., Anjun, N., ... Roux, J. (2013). HMGB1 Accelerates Alveolar Epithelial Repair via an IL-1β- and αvβ6 Integrin-dependent Activation of TGF-β1. PLoS One, 8(5), [e63907]. https://doi.org/10.1371/journal.pone.0063907

HMGB1 Accelerates Alveolar Epithelial Repair via an IL-1β- and αvβ6 Integrin-dependent Activation of TGF-β1. / Pittet, Jean François; Koh, Hidefumi; Fang, Xiaohui; Iles, Karen; Christiaans, Sarah; Anjun, Naseem; Wagener, Brant M.; Park, Dae Won; Zmijewski, Jaroslaw W.; Matthay, Michael A.; Roux, Jérémie.

In: PLoS One, Vol. 8, No. 5, e63907, 16.05.2013.

Research output: Contribution to journalArticle

Pittet, JF, Koh, H, Fang, X, Iles, K, Christiaans, S, Anjun, N, Wagener, BM, Park, DW, Zmijewski, JW, Matthay, MA & Roux, J 2013, 'HMGB1 Accelerates Alveolar Epithelial Repair via an IL-1β- and αvβ6 Integrin-dependent Activation of TGF-β1', PLoS One, vol. 8, no. 5, e63907. https://doi.org/10.1371/journal.pone.0063907
Pittet, Jean François ; Koh, Hidefumi ; Fang, Xiaohui ; Iles, Karen ; Christiaans, Sarah ; Anjun, Naseem ; Wagener, Brant M. ; Park, Dae Won ; Zmijewski, Jaroslaw W. ; Matthay, Michael A. ; Roux, Jérémie. / HMGB1 Accelerates Alveolar Epithelial Repair via an IL-1β- and αvβ6 Integrin-dependent Activation of TGF-β1. In: PLoS One. 2013 ; Vol. 8, No. 5.
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