Beijing Key Laboratory for Animal Genetic Improvement, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Int J Biol Sci. 2018 Jun 3;14(9):1022-1032. doi: 10.7150/ijbs.25275. eCollection 2018.
is one of the most common causal pathogens of mastitis in milk-producing mammals. Toll-like receptor 4 (TLR4) is important for host recognition of this bacteria. Increased activation of TLR4 can markedly enhance the internalization of . In this study, the relationship between TLR4 and mitogen-activated protein kinase (MAPK) signaling pathways in mediating internalization was evaluated in sheep monocytes. Using a TLR4-overexpressing transgenic (Tg) sheep model, we explored the bacterial internalization mechanism in sheep. We found that monocytes of Tg sheep could phagocytize more bacteria and exhibited higher adhesive capacity. The specific inhibition of p38 MAPK or c-Jun N-terminal kinase (JNK) or extracellular signal-regulated kinases (ERKs) reduced TLR4-dependent internalization of bacteria into sheep monocytes. Furthermore, the inhibition of MAPK signaling down-regulated the adhesive capacity of monocytes and the expression of scavenger receptors and adhesion molecules. Taken together, the overexpression of TLR4 in transgenic sheep enhanced the internalization of via MAPK signaling.
是导致产乳哺乳动物乳腺炎的最常见病原体之一。Toll 样受体 4（TLR4）对于宿主识别这种细菌至关重要。TLR4 的过度激活可以显著增强 的内化。在这项研究中，评估了 TLR4 和丝裂原活化蛋白激酶（MAPK）信号通路在介导 内化中的关系在绵羊单核细胞中。使用 TLR4 过表达转基因（Tg）绵羊模型，我们探索了绵羊中细菌内化的机制。我们发现 Tg 绵羊的单核细胞可以吞噬更多的细菌，并且表现出更高的黏附能力。p38 MAPK 或 c-Jun N 端激酶（JNK）或细胞外信号调节激酶（ERK）的特异性抑制减少了 TLR4 依赖性细菌进入绵羊单核细胞的内化。此外，MAPK 信号的抑制降低了单核细胞的黏附能力以及清道夫受体和黏附分子的表达。综上所述，TLR4 在转基因绵羊中的过表达通过 MAPK 信号增强了 的内化。
