Cortisol inhibits NF-κB and MAPK pathways in LPS activated bovine endometrial epithelial cells

The bovine uterus is subject to infection after calving, which may lead to endometritis. Elevated cortisol levels have been observed in postpartum cattle. However, the role of cortisol in the inflammatory response of the uterus has not been reported. The aim of this study was to investigate the anti-inflammatory effects of cortisol on lipopolysaccharide (LPS)-induced primary bovine endometrial epithelial cells (BEECs). BEECs were treated with various concentrations of cortisol (5, 15 and 30 ng/mL) in the presence of LPS. The mRNA expression of TLR4 and proinflammatory cytokines was measured with qPCR. The activation of NF-κB and MAPK signalling pathways was detected with Western blotting and immunofluorescence. Cortisol induced the down-regulation of the mRNA expression of toll-like receptor 4 (TLR4) and proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS). Cortisol inhibited the activity of nuclear factor-κB (NF-κB) via blocking the phosphorylation and degradation of IκB. Cortisol suppressed the phosphorylation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK1/2), p38MAPK and c-Jun N-terminal kinase/stress-activated protein kinase (JNK). These results demonstrated that cortisol may exert its anti-inflammatory actions by regulating NF-κB activation and MAPK phosphorylation.