The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation. Issue 3 (1st June 2020)

• Record Type: Journal Article
• Authors: Rodríguez-López, Gloria Mariana; Soria-Castro, Rodolfo; Campillo-Navarro, Marcia; Pérez-Tapia, Sonia Mayra; Flores-Borja, Fabián; Wong-Baeza, Isabel; Muñoz-Cruz, Samira; López-Santiago, Rubén; Estrada-Parra, Sergio; Estrada-García, Iris; Chávez-Blanco, Alma Delia; Chacón-Salinas, Rommel
• Is Part Of: Journal of leukocyte biology. Volume 108:Issue 3(2020)
• Page Start: 859
• Page End: 866
• Publication Date: 2020-06-01
• Subjects: Fc epsilon receptor I -- mast cell -- phoshoplipase C gamma 2 -- valproic acid; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.3AB0320-547RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: 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. Graphical Abstract: VPA inhibits IgE-mediated mast cell activation and alters PLC-gamma2 phosphorylation