caa a22 4500 445885726 CHVBK 20180317145559.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s00011-010-0278-1 doi (NATIONALLICENCE)springer-10.1007/s00011-010-0278-1 Protective effect of Gö6976, a PKD inhibitor, on LPS/ d -GalN-induced acute liver injury in mice [Elektronische Daten] [G. Duan, J. Zhu, C. Xu, J. Wan, L. Zhang, X. Ge, L. Liu, Y. Liu] Objective: Protein kinase D (PKD) is a newly described serine/threonine protein kinase that plays a pivotal role in inflammatory response. In the present study, we examined the protective effect of Gö6976, a PKD inhibitor, on lipopolysaccharide (LPS) and d-galactosamine (d-GalN)-induced acute liver injury in mice. Materials and methods: Mice were pretreated intraperitoneally with Gö6976 30min before LPS/d-GalN administration . The mortality and degree of hepatic injury was subsequently assessed. Results: The results indicated that LPS/d-GalN administration markedly induced hepatic PKD activation, lethality and liver injury, while pretreatment of the PKD inhibitor Gö6976 significantly inhibited LPS-induced PKD activation, improved the survival of LPS/d-GalN-administered mice and attenuated LPS/d-GalN-induced liver injury, as evidenced by reduced levels of serum aminotransferases as well as reduced histopathological changes. In addition, the protective effects of Gö6976 were paralleled by suppressed activation of mitogen-activated protein kinases (MAPKs), decreased expression of tumor necrosis factor-α (TNF-α) and adhesion molecules, and reduced apoptosis and myeloperoxidase (MPO) activity in liver. Conclusions: Our experimental data indicated that Gö6976, a PKD inhibitor, could effectively prevent LPS/d-GalN-induced acute liver injury by inhibition of MAPKs activation to reduce TNF-α production. This suggests the potential pharmacological value of PKD inhibitors in the intervention of inflammation-based liver diseases. Springer Basel AG, 2010 Protein kinase D nationallicence Lipopolysaccharide nationallicence d -galactosamine nationallicence Inflammation nationallicence Acute liver injury nationallicence Duan G. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut Zhu J. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut Xu C. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut Wan J. Department of Pharmacology, Chongqing Medical University, 400016, Chongqing, China aut Zhang L. Department of Pathophysiology, Chongqing Medical University, 400016, Chongqing, China aut Ge X. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut Liu L. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut Liu Y. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut Inflammation Research SP Birkhäuser Verlag Basel 60/4(2011-04-01), 357-366 1023-3830 60:4<357 2011 60 11 https://doi.org/10.1007/s00011-010-0278-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-010-0278-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Duan G. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut NATIONALLICENCE 700 1- Zhu J. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut NATIONALLICENCE 700 1- Xu C. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut NATIONALLICENCE 700 1- Wan J. Department of Pharmacology, Chongqing Medical University, 400016, Chongqing, China aut NATIONALLICENCE 700 1- Zhang L. Department of Pathophysiology, Chongqing Medical University, 400016, Chongqing, China aut NATIONALLICENCE 700 1- Ge X. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut NATIONALLICENCE 700 1- Liu L. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut NATIONALLICENCE 700 1- Liu Y. Institute of Pathology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/4(2011-04-01), 357-366 1023-3830 60:4<357 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer