PTEN-Foxo1 signaling triggers HMGB1-mediated innate immune responses in acute lung injury

Immunologic Research
Min ZhouGengyun Sun

Abstract

PTEN is a multifunctional phosphatase that regulates immune responses through a PI3K/Akt signaling cascade. HMGB1 plays an important role in the initiation of innate immune responses to induce acute lung injury (ALI). This study was designed to investigate the role of PTEN/Foxo1 signaling in the regulation of in vivo and in vitro innate immune responses in ALI. Using a mouse model of ALI, wild-type (WT) and myeloid-specific PTEN knockout (PTEN(M-KO)) mice were instilled with a recombinant HMGB1 (rHMGB1) or PBS. In some experiments, Foxo1 siRNA or non-specific siRNA was injected into mice 6 h prior to rHMGB1 instillation into lung. We found that rHMGB1 treatment in WT mice increased the expression of PTEN, Foxo1, TLR4, and NF-κB in alveolar macrophages from WT mice. However, macrophage-specific PTEN ablation resulted in reduced Foxo1 and TLR4 while increasing β-catenin (Ser552) and Akt (Ser473) phosphorylation in these cells. Knockdown of Foxo1 with siRNA administration in WT mice ameliorated lung injury and inhibited myeloperoxidase activity followed by rHMGB1 treatment, which was accompanied by decreased mRNA expression coding for TNF-α, IL-1β, MIP2, and IP-10. Moreover, Foxo1 knockdown inhibited the expression of TLR4-depende...Continue Reading

References

Feb 28, 1998·The Journal of Biological Chemistry·S L SchaferP M Pitha
May 4, 2000·The New England Journal of Medicine·L B Ware, M A Matthay
Mar 3, 2001·The New England Journal of Medicine·P E Marik
Dec 6, 2001·American Journal of Respiratory and Critical Care Medicine·W Y ParkT R Martin
Jul 30, 2002·Nature Genetics·David L LewisHans Herweijer
Aug 2, 2002·Cancer Cell·Shivapriya RamaswamyWilliam R Sellers
Mar 28, 2003·Nature Immunology·Shigeo Koyasu
Jan 30, 2004·Journal of Virology·Tomasz I MichalakCarla S Coffin
Sep 18, 2004·American Journal of Respiratory and Critical Care Medicine·Hiroshi UenoAkitoshi Ishizaka
Nov 17, 2005·Oncogene·Joseph R Testa, Philip N Tsichlis
Jul 19, 2006·Nature Reviews. Genetics·Jeffrey A EngelmanLewis C Cantley
Aug 26, 2006·Nature Reviews. Immunology·Kenya Honda, Tadatsugu Taniguchi
Feb 9, 2007·The Journal of Biological Chemistry·Dexing FangZhimin Lu
Apr 9, 2008·Current Opinion in Cell Biology·Dervis A M Salih, Anne Brunet
Nov 20, 2008·Current Protocols in Immunology·Xia ZhangDavid M Mosser
Sep 23, 2009·The Journal of Clinical Investigation·Franco R D'AlessioLandon S King
Jan 22, 2010·Nature·Thomas BeckerMichael Hoch
May 28, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gernot SchabbauerSylvia Knapp
Feb 2, 2012·Nature Reviews. Rheumatology·Helena Erlandsson HarrisDavid S Pisetsky
Oct 20, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Bibo KeJerzy W Kupiec-Weglinski
Jan 15, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Frederik SeilerChristoph Beisswenger
Jul 5, 2013·Nature Reviews. Cancer·Sarah Seton-Rogers
Apr 29, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shi YueYuan Zhai
Jul 13, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emine SahinGernot Schabbauer

❮ Previous
Next ❯

Methods Mentioned

BETA
lavage
electrophoresis
PCR

Related Concepts

Related Feeds

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.