PPARγ mediates selenomethionine-induced suppression of NF-κB signaling in bovine endometrial epithelial cells.

Endometritis in dairy cows is characterized by excessive nuclear factor-κB (NF-κB)-mediated inflammation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key negative regulator of inflammatory signaling. However, whether it mediates the anti-inflammatory effects of selenomethionine (SeMet) in bovine endometrial epithelial cells (BEEC) remains unclear. Here, we investigated the role of PPARγ in SeMet-mediated regulation of lipopolysaccharide (LPS)-induced inflammatory responses. LPS stimulation suppressed PPARγ expression and activated NF-κB signaling, whereas SeMet pretreatment restored PPARγ expression and attenuated NF-κB activation. Functional analyses using lentiviral-mediated knockdown and overexpression demonstrated that PPARγ plays a critical regulatory role in the anti-inflammatory effects mediated by SeMet. PPARγ knockdown exacerbated inflammation and blunted SeMet efficacy, while PPARγ overexpression produced the opposite effects. Furthermore, SeMet-mediated inhibition of p65 phosphorylation and nuclear translocation was dependent on PPARγ expression, with a significant interaction between SeMet treatment and PPARγ status confirmed by two-way ANOVA. Collectively, these findings identify PPARγ as a critical mediator linking selenium to NF-κB signaling and establish a SeMet-PPARγ-NF-κB regulatory axis in BEEC, providing mechanistic support for selenium-based strategies to control endometritis in ruminants.