TGF Presence During IgE-dependent Sensitization Primes Mast Cells for Higher VEGF Production After Fc RI Activation
Juan Pablo Benitez-Garrido1, Alfredo Ibarra-Sanchez1, Marina Macías Silva2, Rafael Villalobos Molina3, Jose Alejandro Padilla-Trejo4, Claudia Gonzalez-Espinosa*, 1
Identifiers and Pagination:Year: 2009
First Page: 16
Last Page: 26
Publisher Id: TOALLJ-2-16
Article History:Received Date: 24/10/2008
Revision Received Date: 16/3/2009
Acceptance Date: 18/3/2009
Electronic publication date: 1/6/2009
Collection year: 2009
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Binding of monomeric Immunoglobulin E (IgE) to the high affinity IgE receptor (FcεRI) on mast cells induces a sensitization process which increases cell survival, augments membrane receptor expression and diminishes activation threshold. Although IgE-dependent sensitization is fundamental for allergic reactions, little is known about the influence of locally produced mediators on the outcome of a posterior allergen challenge. Since Transforming Growth Factorβ (TGFβ) is an important immunomodulator present in most of the tissues where mast cells reside, we decided to analyze the consequences of TGFβ exposure during the sensitization step of mast cells on a posterior IgE-antigen stimulation. Bone Marrow-derived Mast Cells (BMMCs) were sensitized with IgE in the presence or absence of TGFβ. Then, antigen was added and the secretion of the angiogenic cytokine Vascular Endothelial Growth Factor (VEGF) was determined. BMMCs sensitized with IgE+TGFβ showed an increased antigen-induced VEGF secretion compared to those sensitized with IgE alone. Sensitization with IgE+TGFβ did not modify membrane FcεRI receptor expression neither altered antigen-induced degranulation of the cells. Although both IgE and IgE+TGFβ sensitized cells showed an increase in VEGF mRNA stabilization after antigen addition, VEGF mRNA half-life was longer in IgE+TGFβ sensitized cells. p38 MAPK inhibitor SB202196 blocked VEGF mRNA stabilization after antigen addition specially on IgE+TGFβ sensitized cells. These findings suggest that TGFβ presence during the sensitization phase of mast cells can induce modifications to the FcεRI signal transduction system, provoking increased VEGF mRNA stabilization and protein secretion after IgE-antigen stimulation through a p38 MAPK-dependent mechanism.