Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2016; 22(46): 10148-10157
Published online Dec 14, 2016. doi: 10.3748/wjg.v22.i46.10148
C5a/C5aR pathway is essential for up-regulating SphK1 expression through p38-MAPK activation in acute liver failure
Yan-Chang Lei, Chun-Lei Lu, Ling Chen, Ke Ge, Ling-Ling Yang, Wen Li, Yuan-Hua Wu
Yan-Chang Lei, Ling Chen, Ke Ge, Department of Infectious Diseases, Zhejiang Hospital, Hangzhou 310013, Zhejiang Province, China
Yan-Chang Lei, Wen Li, Lingling Yang, Infectious Diseases Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Chun-Lei Lu, Yuan-Hua Wu, The First People’s Hospital of Pinghu, Pinghu 314200, Zhejiang Province, China
Author contributions: Lei YC designed this research; Lei YC, Yang LL, Li W, Lu CL, Chen L and Ge K performed the research and analyzed the data; Lei YC wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81260455 and No. 81160065.
Institutional review board statement: The study was reviewed and approved by the Zhejiang Hospital Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Zhejiang Hospital.
Conflict-of-interest statement: We declare that there are no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Yan-Chang Lei, Chief Physician, Department of Infectious Diseases, Zhejiang Hospital, 12 Lingyin Road, Hangzhou 310013, Zhejiang Province, China. ycleihust@sina.com
Telephone: +86-571-81595081 Fax: +86-571-87980175
Received: August 2, 2016
Peer-review started: August 3, 2016
First decision: August 19, 2016
Revised: September 8, 2016
Accepted: October 10, 2016
Article in press: October 10, 2016
Published online: December 14, 2016
Core Tip

Core tip: Recent studies and our work show that SphK1 and complement activation play an important role in systemic inflammation in acute liver failure (ALF). It has been shown that C5a activates sphingosine kinase 1 (SphK1) in macrophages. However, the mechanism of C5a-induced SphK1 activation is unknown. In this study we found that excessive activation of C5 and up-regulation of C5aR in liver tissue, and the C5a/C5aR pathway is essential for potentiating SphK1 expression through p38 MAPK activation in ALF. To our knowledge, this is the first report of the mechanism of C5a-induced SphK1 activation, which provides a potential immunotherapeutic strategy for ALF in patients.