Mast cells (MCs) play a central role in IgE-dependent immune responses. PPARγis a nuclear receptor that is essential for adipocyte differentiation and insulin sensitivity. Although PPARγis expressed in activated MCs, the effect of PPARγsuppression in IgE-mediated activation of MCs is largely unknown. In the current study, we evaluated the effect of PPARγknockdown on the function of IgE plus antigen (Ag)-stimulated MCs using siRNA-transfected bone marrow-derived MCs (BMMCs). We found that the mRNA expression level of cytokines in IgE/Ag-stimulated BMMCs was significantly increased in PPARγknockdown BMMCs, and IgE/Ag-mediated degranulation and the protein production level of TNF-α was moderately increased by PPARγknockdown, whereas the cell surface expression level of FcϵRI was not affected by PPARγknockdown. Oral administration of pioglitazone (PPARγagonist) significantly suppressed body temperature change of mice in passive systemic anaphylaxis, supporting the inhibitory functions of PPARγin IgE/Ag-dependent activation of MCs in vivo. IgE-mediated up-regulation of mRNA levels of Ptgs2 (encoding COX-2) was drastically enhanced in PPARγknockdown BMMCs. Although several prostaglandin (PG) derivatives are known to be ligands for PPARγ, treatment with a COX inhibitor, acetyl salicylic acid, up-regulated the IgE-mediated increase of Il13, Tnf and Ptgs2 mRNA levels in a synergistic manner with PPARγsiRNA. Knockdown of COX-1 and/or COX-2 by siRNA showed that suppression of IgE/Ag-mediated activation was mainly dependent on COX-1. Taken together, these results indicate that PPARγsuppresses IgE/Ag-induced transactivation of cytokine genes and the Ptgs2 gene in MCs in a manner distinguishable from that of PGs.
CITATION STYLE
Nagata, K., Kasakura, K., Miura, R., Yashiro, T., & Nishiyama, C. (2019). Suppressive role of PPARγin the IgE-dependent activation of mast cells. International Immunology, 32(2), 143–150. https://doi.org/10.1093/intimm/dxz069
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