Doxycycline Induces Mitophagy and Suppresses Production of Interferon-ß in IPEC-J2 Cells

Xing, Yang; Liqi, Zhu; Jian, Lin; Qinghua, Yu; Qian, Yang

With the rapid development of the breeding industry, an increasing number of antibiotics are being used as veterinary drugs and feed additives (Du and Liu, 2012) . Depending on the types and sizes of animals and the type of antibiotic, the dose of antibiotic varies from 3.0 to 220.0 g/kg of feed (McEwen and Fedorka-Cray, 2002) . Doxycycline (DOX) is a second-generation tetracycline derivative used widely in pig husbandry (Zhang et al., 2015) . It is reported that the concentration of DOX in swine manure that collected from different developing phases of livestock in 4 typical farms of Tianjin, China, were in the range of 8.6-59.8 mg/kg (Xian-Gang et al., 2008) . In fact, very high concentration of veterinary antibiotics (up to hundreds of mg/kg) have frequently been found in animal excreta in China (Chen et al., 2012) . According to the drug specifications of commercial doxycycline, the recommended usage does of DOX is in the range of 100-200 mg/kg of feed or water in China. It occupies the A-site of the bacterial 30S ribosomal subunit and blocks recruitment of aminoacyl-tRNA into the bacterial ribosome, which inhibits protein synthesis (Chopra, 1994) . Given the proteobacterial origin of mitochondria, DOX also has powerful inhibitory effects on mitochondrial ribosomes and protein synthesis . This antibiotic can destroy mitochondrial dynamics and promotes the accumulation of dysfunctional mitochondria in cells (Moullan et al., 2015) .