Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2016; 22(31): 6965-6971
Published online Aug 21, 2016. doi: 10.3748/wjg.v22.i31.6965
Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic steatohepatitis?
Priya Handa, Akhila Vemulakonda, Kris V Kowdley, Misael Uribe, Nahum Méndez-Sánchez
Priya Handa, Akhila Vemulakonda, Kris V Kowdley, Senior Research Scientist, Organ Care Research and Liver Care Network, Swedish Medical Center, Seattle, WA 98104, United States
Misael Uribe, Nahum Mendez-Sanchez, Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City 07510, Mexico
Author contributions: Handa P wrote the manuscript; Vemulakonda A, Kowdley KV and Méndez-Sánchez N contributed intellectual content to the revision of the manuscript; all authors contributed to the manuscript.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
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: Priya Handa, MS, PhD, Senior Research Scientist, Organ Care Research and Liver Care Network, 1124 Columbia Street, Suite 600, Swedish Medical Center, Seattle, WA 98104, United States. priya.handa@swedish.org
Telephone: +1-206-3862531 Fax: +1-206-2152126
Received: April 7, 2016
Peer-review started: April 7, 2016
First decision: May 12, 2016
Revised: June 2, 2016
Accepted: June 28, 2016
Article in press: June 28, 2016
Published online: August 21, 2016
Core Tip

Core tip: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease. It has been shown that innate immune activation contributes to the progression of NAFLD by inducing hepatic inflammation. A new study recently demonstrated that hepatocyte mitochondrial DNA acts as a damage -induced molecular pattern activating hepatic TLR9 to initiate and amplify inflammatory signaling leading to nonalcoholic steatohepatitis (NASH). Inhibiting TLR9 by using a synthetic antagonist, IRS 954, reversed steatohepatitis; as did a whole body ablation of TLR9 or a myeloid-specific knockout of TLR9. This editorial summarizes the findings of the new study and describes potential novel therapeutic targets that may hold promise for NASH treatment.