Over-expression of Toll-like receptor 2 up-regulates heme oxygenase-1 expression and decreases oxidative injury in dairy goats

Abstract

BackgroundMastitis, an infection caused by Gram-positive bacteria, produces udder inflammation and oxidative injury in milk-producing mammals. Toll-like receptor 2 (TLR2) is important for host recognition of invading Gram-positive microbes. Over-expression of TLR2 in transgenic dairy goats is a useful model for studying various aspects of infection with Gram-positive bacteria, in vivo.MethodsWe over-expressed TLR2 in transgenic dairy goats. Pam3CSK4, a component of Gram-positive bacteria, triggered the TLR2 signal pathway by stimulating the monocytes-macrophages from the TLR2-positive transgenic goats, and induced over-expression of activator protein-1 (AP-1), phosphatidylinositol 3-kinase (PI3K) and transcription factor nuclear factor kappa B (NF-κB) and inflammation factors downstream of the signal pathway.ResultsCompared with wild-type controls, measurements of various oxidative stress-related molecules showed that TLR2, when over-expressed in transgenic goat monocytes-macrophages, resulted in weak lipid damage, high level expression of anti-oxidative stress proteins, and significantly increased mRNA levels of transcription factor NF-E2-related factor-2 (Nrf2) and the downstream gene, heme oxygenase-1 (HO-1). When Pam3CSK4 was used to stimulate ear tissue in vivo the HO-1 protein of the transgenic goats had a relatively high expression level.ConclusionsThe results indicate that the oxidative injury in goats over-expressing TLR2 was reduced following Pam3CSK4 stimulation. The underlying mechanism for this reduction was increased expression of the anti-oxidation gene HO-1 by activation of the Nrf2 signal pathway.

Sodium butyrate ameliorates lipopolysaccharide‐induced cow mammary epithelial cells from oxidative stress damage and apoptosis

“…Cow subclinical mastitis is an inflammatory response of the udder, which is characterized by pathological alterations in the mammary gland and physiochemical changes in milk. In cow subclinical mastitis, oxidative stress occurs due to infection by pathogens that trigger immune response and induce ROS generation in cells …”

Prototheca zopfii isolated from bovine mastitis induced oxidative stress and apoptosis in bovine mammary epithelial cells

“…In bovine mastitis, oxidative stress occurs due to infection of pathogen that triggers the immune response and induces the reactive oxygen species (ROS) generation in cells [ 14 ]. The proliferation and apoptosis of bovine mammary epithelial cells (bMECs) under oxidative stress are modulated by cellular antioxidant status [ 15 ].…”

Overexpression of Toll-Like Receptor 4 Contributes to Phagocytosis of Salmonella Enterica Serovar Typhimurium via Phosphoinositide 3-Kinase Signaling in Sheep

“…After incubation for 2 h at 37°C in a 5% CO 2 incubator, the non-adherent cells were removed by washing three times with phosphate-buffered saline (PBS). The adherent cells were then cultivated in RPMI1640 (Gibco, Grand Island, NY, USA) medium containing 10% FBS (Gibco), and the cells were incubated at 37°C in a 5% CO 2 incubator for 48 h, changing the medium every 24 h. After 48 h of incubation and washing off non-adherent cells, the adherent cells were mainly composed of monocytemacrophages [11].…”

“…TLR4 is mainly expressed in monocytes/macrophages and epithelial cells in sheep; it is also abundant in peripheral blood monocytes [11]. Lipopolysaccharide (LPS) is the most common ligand of TLR4 and is also the major component of the cell wall of Gram-negative bacteria such as Salmonella.…”