Aspirin alleviates hepatic fibrosis by suppressing hepatic stellate cells activation via the TLR4/NF-κB pathway.

Yan Liu,Lixia Duan,Yuxian Jia,Aihua Tan,Li Nong,Jinmin Zhao,Yongkui Lu

doi:10.18632/aging.103002

Abstract

Hepatic fibrosis arises from a sustained wound-healing response to chronic liver injury. Because the occurrence and development of hepatic fibrosis is always associated with chronic inflammation, controlling inflammation within the liver may be an effective means of controlling the development and progression of hepatic fibrosis. Aspirin is a non-steroidal anti-inflammatory drug used to relieve both inflammatory symptoms and pain. The results of our study showed that aspirin significantly attenuated hepatic inflammation and fibrosis. Aspirin effectively inhibited the activation and proliferation of hepatic stellate cells (HSCs), which led to downregulation of inflammatory factors, including IL-6 and TNF-α in those cells. Aspirin also downregulated expression of Toll-like receptor-4 (TLR4) on HSCs, as well as its downstream mediators, MyD88 and NF-κB. The results of our study demonstrate aspirin’s potential to inhibit the development of hepatic fibrosis and the molecular mechanism by which it acts. They suggest aspirin may be an effective therapeutic agent for the treatment of hepatic fibrosis.

Highlights

Hepatic fibrosis is a consequence of a sustained woundhealing response to chronic liver damage
These findings suggest that aspirin treatment reduces hepatic inflammation and damage in this rat model
Hepatic fibrosis arises from wound healing in response to chronic inflammation within the liver [13, 14]

Summary

Introduction

Hepatic fibrosis is a consequence of a sustained woundhealing response to chronic liver damage. Because chronic inflammation with the liver is associated with the occurrence of hepatic fibrosis, controlling inflammation could be an effective strategy for controlling the development of hepatic fibrosis. It has been reported that aspirin prevents the development of fibrosis [2, 3], though the mechanism remains unclear. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and play an important role in leading inflammatory responses [5]. The binding of lipopolysaccharide (LPS) to TLR4 within the liver initiates an inflammatory response that results in inflammation-associated liver damage [7,8,9]. We examined the effect of aspirin on carbon www.aging-us.com tetrachloride (CCl4)-induced hepatic fibrosis and explored the potential mechanism

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Conclusion