Role of PTEN in neutrophil extracellular trap formation

Shahram Teimourian; Ehsan Moghanloo

doi:10.1016/j.molimm.2015.03.251

Role of PTEN in neutrophil extracellular trap formation

Mol Immunol. 2015 Aug;66(2):319-24. doi: 10.1016/j.molimm.2015.03.251. Epub 2015 Apr 26.

Authors

Shahram Teimourian¹, Ehsan Moghanloo²

Affiliations

¹ Department of Medical Genetics, Iran University of Medical Sciences, Tehran, Iran; Department of Human Genetics, Tehran University of Medical Sciences, Tehran, Iran; Pediatrics Infectious Diseases Research Center, Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: teimourian.sh@iums.ac.ir.
² Department of Human Genetics, Tehran University of Medical Sciences, Tehran, Iran; Pediatrics Infectious Diseases Research Center, Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

PMID: 25913476
DOI: 10.1016/j.molimm.2015.03.251

Abstract

NETosis has been associated with a particular mode of cell death although it is still controversial as to what extent autophagy is involved in NETosis. Class I/AKT/mTOR pathway is a key regulator of autophagy. PTEN tumor suppressor gene encodes a dual specificity phosphatase that antagonizes the phosphatidylinositol 3-kinase in class the I/AKT/mTOR pathway. In this study, we investigated the effects of PTEN down-regulation as well as overexpression on NETosis. Our results show that 35% of HL-60 differentiated neutrophil-like cells generated NETs by PMA. The portion of the population that produced NETs in PTEN knockdown HL-60 differentiated neutrophils was 9% and in PTEN overexpressed HL-60 differentiated neutrophils, it was 56%. Our results show that increasing PTEN expression increases NETs formation in neutrophils, and its suppression reduces NETs.

Keywords: Autophagy; NETosis; Neutrophil extracellular traps; PTEN.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Death / immunology
Cell Differentiation
Class I Phosphatidylinositol 3-Kinases / genetics
Class I Phosphatidylinositol 3-Kinases / immunology
Extracellular Traps / genetics
Extracellular Traps / immunology*
Gene Expression Regulation
HL-60 Cells
Humans
Neutrophils / drug effects
Neutrophils / immunology*
Neutrophils / pathology
PTEN Phosphohydrolase / agonists
PTEN Phosphohydrolase / antagonists & inhibitors
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / immunology*
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / immunology
RNA, Small Interfering / genetics
RNA, Small Interfering / immunology
Signal Transduction
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / immunology
Tetradecanoylphorbol Acetate / pharmacology

Substances

RNA, Small Interfering
MTOR protein, human
Class I Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
PTEN Phosphohydrolase
PTEN protein, human
Tetradecanoylphorbol Acetate