TGFβ Presence During IgE-dependent Sensitization Primes Mast Cells for Higher VEGF Production After FcεRI Activation
Juan Pablo Benitez-Garrido, Alfredo Ibarra-Sanchez, Marina Macias Silva, Rafael Villalobos Molina, Jose Alejandro Padilla-Trejo, Claudia Gonzalez-Espinosa
The Open Allergy Journal
Binding of monomeric Immunoglobulin E (IgE) to the high affinity IgE receptor (Fc RI) 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 Factor (TGF ) is an important
... r present in most of the tissues where mast cells reside, we decided to analyze the consequences of TGF 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 TGF . Then, antigen was added and the secretion of the angiogenic cytokine Vascular Endothelial Growth Factor (VEGF) was determined. BMMCs sensitized with IgE+TGF showed an increased antigen-induced VEGF secretion compared to those sensitized with IgE alone. Sensitization with IgE+TGF did not modify membrane Fc RI receptor expression neither altered antigen-induced degranulation of the cells. Although both IgE and IgE+TGF sensitized cells showed an increase in VEGF mRNA stabilization after antigen addition, VEGF mRNA half-life was longer in IgE+TGF sensitized cells. p38 MAPK inhibitor SB202196 blocked VEGF mRNA stabilization after antigen addition specially on IgE+TGF sensitized cells. These findings suggest that TGF presence during the sensitization phase of mast cells can induce modifications to the Fc RI signal transduction system, provoking increased VEGF mRNA stabilization and protein secretion after IgE-antigen stimulation through a p38 MAPK-dependent mechanism. © Benitez-Garrido et al.; Licensee Bentham Open. This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.