Anti-Apoptotic Bfl-1 Is the Major Effector in Activation-Induced Human Mast Cell Survival

Mast cells are best known for their role in allergic reactions, where aggregation of FcεRI leads to the release of mast cell mediators causing allergic symptoms. The activation also induces a survival program in the cells, i.e., activation-induced mast cell survival. The aim of the present study was...

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Main Authors:	Ekoff, Maria, Lyberg, Katarina, Krajewska, Maryla, Arvidsson, Monica, Rak, Sabina, Reed, John C., Harvima, Ilkka, Nilsson, Gunnar
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376125/

id	pubmed-3376125
recordtype	oai_dc
spelling	pubmed-33761252012-06-20 Anti-Apoptotic Bfl-1 Is the Major Effector in Activation-Induced Human Mast Cell Survival Ekoff, Maria Lyberg, Katarina Krajewska, Maryla Arvidsson, Monica Rak, Sabina Reed, John C. Harvima, Ilkka Nilsson, Gunnar Research Article Mast cells are best known for their role in allergic reactions, where aggregation of FcεRI leads to the release of mast cell mediators causing allergic symptoms. The activation also induces a survival program in the cells, i.e., activation-induced mast cell survival. The aim of the present study was to investigate how the activation-induced survival is mediated. Cord blood-derived mast cells and the mast cell line LAD-2 were activated through FcεRI crosslinking, with or without addition of chemicals that inhibit the activity or expression of selected Bcl-2 family members (ABT-737; roscovitine). Cell viability was assessed using staining and flow cytometry. The expression and function of Bcl-2 family members BFL-1 and MCL-1 were investigated using real-time quantitative PCR and siRNA treatment. The mast cell expression of Bfl-1 was investigated in skin biopsies. FcεRI crosslinking promotes activation-induced survival of human mast cells and this is associated with an upregulation of the anti-apoptotic Bcl-2 family member Bfl-1. ABT-737 alone or in combination with roscovitine decreases viability of human mast cells although activation-induced survival is sustained, indicating a minor role for Bcl-XL, Bcl-2, Bcl-w and Mcl-1. Reducing BFL-1 but not MCL-1 levels by siRNA inhibited activation-induced mast cell survival. We also demonstrate that mast cell expression of Bfl-1 is elevated in birch-pollen-provocated skin and in lesions of atopic dermatitis and psoriasis patients. Taken together, our results highlight Bfl-1 as a major effector in activation-induced human mast cell survival. Public Library of Science 2012-06-15 /pmc/articles/PMC3376125/ /pubmed/22720045 http://dx.doi.org/10.1371/journal.pone.0039117 Text en Ekoff et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ekoff, Maria Lyberg, Katarina Krajewska, Maryla Arvidsson, Monica Rak, Sabina Reed, John C. Harvima, Ilkka Nilsson, Gunnar
spellingShingle	Ekoff, Maria Lyberg, Katarina Krajewska, Maryla Arvidsson, Monica Rak, Sabina Reed, John C. Harvima, Ilkka Nilsson, Gunnar Anti-Apoptotic Bfl-1 Is the Major Effector in Activation-Induced Human Mast Cell Survival
author_facet	Ekoff, Maria Lyberg, Katarina Krajewska, Maryla Arvidsson, Monica Rak, Sabina Reed, John C. Harvima, Ilkka Nilsson, Gunnar
author_sort	Ekoff, Maria
title	Anti-Apoptotic Bfl-1 Is the Major Effector in Activation-Induced Human Mast Cell Survival
title_short	Anti-Apoptotic Bfl-1 Is the Major Effector in Activation-Induced Human Mast Cell Survival
title_full	Anti-Apoptotic Bfl-1 Is the Major Effector in Activation-Induced Human Mast Cell Survival
title_fullStr	Anti-Apoptotic Bfl-1 Is the Major Effector in Activation-Induced Human Mast Cell Survival
title_full_unstemmed	Anti-Apoptotic Bfl-1 Is the Major Effector in Activation-Induced Human Mast Cell Survival
title_sort	anti-apoptotic bfl-1 is the major effector in activation-induced human mast cell survival
description	Mast cells are best known for their role in allergic reactions, where aggregation of FcεRI leads to the release of mast cell mediators causing allergic symptoms. The activation also induces a survival program in the cells, i.e., activation-induced mast cell survival. The aim of the present study was to investigate how the activation-induced survival is mediated. Cord blood-derived mast cells and the mast cell line LAD-2 were activated through FcεRI crosslinking, with or without addition of chemicals that inhibit the activity or expression of selected Bcl-2 family members (ABT-737; roscovitine). Cell viability was assessed using staining and flow cytometry. The expression and function of Bcl-2 family members BFL-1 and MCL-1 were investigated using real-time quantitative PCR and siRNA treatment. The mast cell expression of Bfl-1 was investigated in skin biopsies. FcεRI crosslinking promotes activation-induced survival of human mast cells and this is associated with an upregulation of the anti-apoptotic Bcl-2 family member Bfl-1. ABT-737 alone or in combination with roscovitine decreases viability of human mast cells although activation-induced survival is sustained, indicating a minor role for Bcl-XL, Bcl-2, Bcl-w and Mcl-1. Reducing BFL-1 but not MCL-1 levels by siRNA inhibited activation-induced mast cell survival. We also demonstrate that mast cell expression of Bfl-1 is elevated in birch-pollen-provocated skin and in lesions of atopic dermatitis and psoriasis patients. Taken together, our results highlight Bfl-1 as a major effector in activation-induced human mast cell survival.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376125/
_version_	1611537115866202112

Anti-Apoptotic Bfl-1 Is the Major Effector in Activation-Induced Human Mast Cell Survival

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