Barna Réka Fanni, Mackei Máté, Pászti-Gere Erzsébet, Neogrády Zsuzsanna, Jerzsele Ákos, Mátis Gábor
Division of Biochemistry, Department of Physiology and Biochemistry, University of Veterinary Medicine, 1078 Budapest, Hungary.
Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest, 1078 Budapest, Hungary.
Biomedicines. 2021 Apr 21;9(5):450. doi: 10.3390/biomedicines9050450.
The function of the transmembrane serine protease matriptase is well described in mammals, but it has not been elucidated in avian species yet. Hence, the aim of the present study was to assess the effects of the 3-amidinophenylalanine (3-AphA)-type matriptase inhibitors MI432 and MI460 on the inflammatory and oxidative state of chicken primary hepatocyte mono-cultures and hepatocyte-nonparenchymal cell co-cultures, the latter serving as a proper model of hepatic inflammation in birds. Cell cultures were exposed to MI432 and MI460 for 4 and 24 h at 10, 25, and 50 µM concentrations, and thereafter the cellular metabolic activity, extracellular interleukin (IL-)6, IL-8, HO and malondialdehyde concentrations were monitored. Both inhibitors caused a transient moderate reduction in the metabolic activity following 4 h exposure, which was restored after 24 h, reflecting the fast hepatic adaptation potential to matriptase inhibitor administration. Furthermore, MI432 triggered an intense elevation in the cellular proinflammatory IL-6 and IL-8 production after both incubation times in all concentrations, which was not coupled to enhanced oxidative stress and lipid peroxidation based on unchanged HO production, malondialdehyde levels and glutathione peroxidase activity. These data suggest that physiological matriptase activities might have a key function in retaining the metabolic and inflammatory homeostasis of the liver in chicken, without being a major modulator of the hepatocellular redox state.
跨膜丝氨酸蛋白酶matriptase在哺乳动物中的功能已得到充分描述，但在鸟类中尚未阐明。因此，本研究的目的是评估3-脒基苯丙氨酸（3-AphA）型matriptase抑制剂MI432和MI460对鸡原代肝细胞单培养物和肝细胞-非实质细胞共培养物的炎症和氧化状态的影响，后者可作为鸟类肝脏炎症的合适模型。将细胞培养物分别用浓度为10、25和50 μM的MI432和MI460处理4小时和24小时，然后监测细胞代谢活性、细胞外白细胞介素（IL-）6、IL-8、HO和丙二醛浓度。两种抑制剂在处理4小时后均导致代谢活性短暂适度降低，但在24小时后恢复，这反映了肝脏对matriptase抑制剂给药的快速适应潜力。此外，在所有浓度下，MI432在两个孵育时间后均引发细胞促炎IL-6和IL-8产生的强烈升高，基于HO产生、丙二醛水平和谷胱甘肽过氧化物酶活性不变，这与氧化应激和脂质过氧化增强无关。这些数据表明，生理matriptase活性可能在维持鸡肝脏的代谢和炎症稳态中起关键作用，而不是肝细胞氧化还原状态的主要调节因子。
