Plant Defensin γ-Thionin Induces MAPKs and Activates Histone Deacetylases in Bovine Mammary Epithelial Cells Infected With Staphylococcus aureus

Defensins are an important group of host defense peptides. They have immunomodulatory properties, which have been mainly described for mammal defensins, but similar effects for plant defensins remain unknown. Previously, we showed that the defensin gamma-thionin (Capsicum chinense) reducesStaphylococcus aureusinternalization into bovine mammary epithelial cells (bMECs) while inducing Toll-like receptor 2 (TLR2), modulating the inflammatory response. Here, we analyze the effect of gamma-thionin on the TLR2 pathway in bMECs infected withS. aureusand determine if it modulates epigenetic marks. Pre-treated bMECs with gamma-thionin (100 ng/ml) reduced the basal activation of p38 and ERK1/2 (similar to 3-fold), but JNK was increased (similar to 1.5-fold). Also, infected bMECs induced p38, but this effect was reversed by gamma-thionin, whereas ERK1/2 was reduced by infection but stimulated by gamma-thionin. Likewise, gamma-thionin reduced the activation of Akt kinase similar to 50%. Furthermore, gamma-thionin induced the activation of transcriptional factors of inflammatory response, highlighting EGR, E2F-1, AP-1, and MEF, which were turned off by bacteria. Also, gamma-thionin induced the activation of histone deacetylases (HDACs, similar to 4-fold) at 24 h in infected bMECs and reduced LSD1 demethylase (HDMs, similar to 30%) activity. Altogether, these results demonstrated the first time that a plant defensin interferes with inflammatory signaling pathways in mammalian cells.