Anti-inflammatory Effect And Regulation Of Inflammatory Signal Transduction Pathway Of Selenium On Bovine Mastitis

Bovine mastitis is characterized by inflammation and pathological changes in theudder tissues caused by mammary gland inflammation; as a result, milk yield isreduced, milk quality is compromised, and veterinary costs are increased, therebycausing worldwide economic losses in the dairy industry. The essential trace elementselenium (Se), in the form of selenoproteins, plays a pivotal role in the antioxidantdefense system of the cell，acts as modulator of inflammatory response in infectiousand autoimmune disease. A known consequence that Se-deficiency has beenassociated with increased clinical mastitis cases. So we explored theanti-inflammatory effects and associated mechanisms of selenium on bovine mastitis.These results provided theoretical foundation and the basis of experimental data forprophylaxis and treatment of bovine mastitis.The main pathogen of clinical bovine mastitis is E.coli. Lipopolysaccharide (LPS)is a powerful bacterial virulence factor of E.coli. The model of LPS-induced mousemastitis is recognized as a valuable tool to study the effects of bovine mastitis becausethey mimic the responses observed during natural mastitis. First, effects of diaryselenium levels on LPS-induced models of mouse mastitis were investigated. Theanimals were fed with diaries that contain the different selenium level. At the end ofexperiment, an intramammary infusion of LPS was used to establish mouse mastitismodel.Histopathological analysis, enzymatic activity test and pro-inflammatory genesanalysis were conducted to study effects of diary selenium levels on LPS-inducedmouse mammary mastitis. Results showed that activity of glutathione peroxidase andmRNA expression of GPX1、GPX4of mammary gland was affected by diaryselenium levels in a dose depended way. Histopathological observation of mammarygland in LPS-induced Se-deficient mouse mammary gland showed more infiltrationof inflammatory cells. Pro-inflammatory genes expression levels in mammary glandof Se-deficient group were higher than Se-adequate group. These results showed that LPS-induced inflammatory responses of mammary gland were affected by diary Selevels. NF-κB activity might be involved in these processes.Second, in vitro inflammatory model was performed by LPS-stimulated primarymouse mammary gland epithelial cells. We investigated the effect of differentconcentrations of Na2SeO3on LPS-induced cytokines, inflammatory mediator,mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB). Resultsshowed that Na2SeO3inhibited LPS-stimulated TNF-α secretion but not IL-6or IL-1β.Na2SeO3inhibited LPS-stimulated NF-κB activity, p38, ERK and JNK MAPKsphosphorylation.Finally, in vitro inflammatory model was performed by LPS-induced primarybovine epithelial cells. Different concentration of Na2SeO3was added in cell culturemedia. TLR4expression and regarding down stream signal molecules and cytokinesin LPS-stimulated bovine epithelial cell were investigated. Results showed that TLR4,NF-κB and down stream cytokines expression were up regulated after LPSstimulation. Na2SeO3inhibited LPS-stimulated downstream cytokines expression byinhibit NF-κB expression.