The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation

Gloria Mariana Rodríguez-López, Rodolfo Soria-Castro, Marcia Campillo-Navarro, Sonia Mayra Pérez-Tapia, Fabián Flores-Borja, Isabel Wong-Baeza, Samira Muñoz-Cruz, Rubén López-Santiago, Sergio Estrada-Parra, Iris Estrada-García, Alma Delia Chávez-Blanco, Rommel Chacón-Salinas

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

©2020 Society for Leukocyte Biology Mast cell activation through the high-affinity IgE receptor (FcεRI) plays a central role in allergic reactions. FcεRI-mediated activation triggers multiple signaling pathways leading to degranulation and synthesis of different inflammatory mediators. IgE-mediated mast cell activation can be modulated by different molecules, including several drugs. Herein, we investigated the immunomodulatory activity of the histone deacetylase inhibitor valproic acid (VPA) on IgE-mediated mast cell activation. To this end, bone marrow-derived mast cells (BMMC) were sensitized with IgE and treated with VPA followed by FcεRI cross-linking. The results indicated that VPA reduced mast cell IgE-dependent degranulation and cytokine release. VPA also induced a significant reduction in the cell surface expression of FcεRI and CD117, but not other mast cell surface molecules. Interestingly, VPA treatment inhibited the phosphorylation of PLCγ2, a key signaling molecule involved in IgE-mediated degranulation and cytokine secretion. However, VPA did not affect the phosphorylation of other key components of the FcεRI signaling pathway, such as Syk, Akt, ERK1/2, or p38. Altogether, our data demonstrate that VPA affects PLCγ2 phosphorylation, which in turn decreases IgE-mediated mast cell activation. These results suggest that VPA might be a key modulator of allergic reactions and might be a promising therapeutic candidate.
Original languageAmerican English
JournalJournal of Leukocyte Biology
DOIs
StatePublished - 1 Jan 2020

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