College of Life Sciences, Inner Mongolia University , Hohhot, People's Republic of China .
DNA Cell Biol. 2014 Jun;33(6):388-97. doi: 10.1089/dna.2013.2195. Epub 2014 Feb 24.
Infections with Staphylococcus aureus, a common inducer of mastitis, often result in mammary gland damage and death of various cell types. Although S. aureus was suggested to induce apoptosis in a bovine mammary epithelial cell (BMEC) line, MAC-T, it is unknown whether primary BMECs (pBMECs) apoptosis is triggered by S. aureus and the associated underlying molecular mechanisms have not been determined. Here, we demonstrated that S. aureus induced apoptosis in pBMECs in a time- and dose-dependent manner. Further, S. aureus-induced apoptosis in pBMECs was associated with activation of caspase-3 and caspase-8, but caspase-9 was not. In addition, pBMECs apoptosis was mitigated by caspase-3 and caspase-8 inhibitors, suggesting that apoptosis is initiated via caspase-8 activation. Moreover, S. aureus infection significantly increased expressions of Fas and Fas-associated death domain (FADD) of pBMECs. Taken together, our results demonstrated that S. aureus induced apoptosis in pBMECs via the Fas-FADD death receptor and subsequently triggered the caspase-8-dependent signaling.
金黄色葡萄球菌(Staphylococcus aureus)感染是乳腺炎的常见诱因,常导致乳腺组织损伤和各种细胞类型死亡。尽管金黄色葡萄球菌被认为能诱导牛乳腺上皮细胞(bovine mammary epithelial cell,BMEC)系 MAC-T 细胞发生凋亡,但尚不清楚金黄色葡萄球菌是否能诱导原代 BMEC(primary BMEC,pBMEC)发生凋亡,也不清楚其相关的潜在分子机制。本研究表明,金黄色葡萄球菌能以时间和剂量依赖的方式诱导 pBMEC 发生凋亡。此外,金黄色葡萄球菌诱导的 pBMEC 凋亡与 caspase-3 和 caspase-8 的激活有关,但 caspase-9 无关。另外,caspase-3 和 caspase-8 抑制剂可减轻 pBMEC 凋亡,提示凋亡是通过 caspase-8 激活而引发的。此外,金黄色葡萄球菌感染显著增加了 pBMEC 中 Fas 和 Fas 相关死亡结构域(Fas-associated death domain,FADD)的表达。综上,本研究结果表明,金黄色葡萄球菌通过 Fas-FADD 死亡受体诱导 pBMEC 发生凋亡,并随后触发 caspase-8 依赖性信号通路。