TY - JOUR
T1 - The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation
AU - Rodríguez-López, Gloria Mariana
AU - Soria-Castro, Rodolfo
AU - Campillo-Navarro, Marcia
AU - Pérez-Tapia, Sonia Mayra
AU - Flores-Borja, Fabián
AU - Wong-Baeza, Isabel
AU - Muñoz-Cruz, Samira
AU - López-Santiago, Rubén
AU - Estrada-Parra, Sergio
AU - Estrada-García, Iris
AU - Chávez-Blanco, Alma Delia
AU - Chacón-Salinas, Rommel
N1 - Publisher Copyright:
©2020 Society for Leukocyte Biology
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
KW - Fc epsilon receptor I
KW - mast cell
KW - phoshoplipase C gamma 2
KW - valproic acid
UR - http://www.scopus.com/inward/record.url?scp=85085895080&partnerID=8YFLogxK
U2 - 10.1002/JLB.3AB0320-547RR
DO - 10.1002/JLB.3AB0320-547RR
M3 - Artículo
C2 - 32480423
SN - 0741-5400
VL - 108
SP - 859
EP - 866
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -