Cutting Edge: Lentiviral short hairpin RNA silencing of PTEN in human mast cells reveals constitutive signals that promote cytokine secretion and cell survival

The Journal of Immunology : Official Journal of the American Association of Immunologists
Yasuko FurumotoJuan Rivera

Abstract

Engagement of the FcepsilonRI expressed on mast cells induces the production of phosphatidylinositol 3, 4, 5-trisphosphate by PI3K, which is essential for the functions of the cells. PTEN (phosphatase and tensin homologue deleted on chromosome ten) directly opposes PI3K by dephosphorylating phosphatidylinositol 3, 4, 5-trisphosphate at the 3' position. In this work we used a lentivirus-mediated short hairpin RNA gene knockdown method to study the role of PTEN in CD34(+) peripheral blood-derived human mast cells. Loss of PTEN caused constitutive phosphorylation of Akt, p38 MAPK, and JNK, as well as cytokine production and enhancement in cell survival, but not degranulation. FcepsilonRI engagement of PTEN-deficient cells augmented signaling downstream of Src kinases and increased calcium flux, degranulation, and further enhanced cytokine production. PTEN-deficient cells, but not control cells, were resistant to inhibition of cytokine production by wortmannin, a PI3K inhibitor. The findings demonstrate that PTEN functions as a key regulator of mast cell homeostasis and FcepsilonRI-responsiveness.

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Citations

May 15, 2007·Immunological Reviews·Jakub Abramson, Israel Pecht
Nov 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Norifumi SawamukaiYoshiya Tanaka
Jul 10, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yumi YamashitaJuan Rivera
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Apr 24, 2014·BioMed Research International·Chiou-Feng LinChiung-Wen Tsao
May 15, 2007·Immunological Reviews·Juan Rivera, Ana Olivera
May 21, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Juan ZhangReuben P Siraganian
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Aug 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erola Ainsua-EnrichMargarita Martín
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Nov 23, 2017·Frontiers in Immunology·Yi-Gen PanChing-Liang Chu
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Jan 10, 2021·Molecular Immunology·Yizhao SunZhongcheng Liu
Sep 9, 2008·Trends in Immunology·Mi-Sun KimAlasdair M Gilfillan

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