Protective Effects of Lactic Acid Bacteria Against TLR4 Induced Inflammatory Response in Hepatoma HepG2 Cells Through Modulation of Toll-Like Receptor Negative Regulators of Mitogen-Activated Protein Kinase and NF-κB Signaling.

Paulraj Kanmani,Hojun Kim

doi:10.3389/fimmu.2018.01537

Abstract

The beneficial effects of probiotics in several liver diseases have been investigated in both animal and clinical models; however, the precise mechanisms responsible for their effects have not yet been elucidated. Gut transmitted endotoxins such as LPS have been shown to play critical roles in hepatic inflammation and injury. Therefore, in this study, we investigated the beneficial role of selected lactic acid bacteria (LABs) on reduction of hepatic steatosis (HS) and attenuation of LPS induced inflammatory response in vitro. Total cellular fluid (TCF) of LABs treatment reduced HS by decreasing the amount of lipid accumulation in vitro. Additionally, HepG2 cells exposed to LPS showed increased expression of exacerbated inflammatory cytokines, such as IL-6, CXCL8, CCL2, and TNF-α, but these effects were counteracted when cells were treated with TCF of LABs prior to LPS challenge. Moreover, TCF of LABs was able to modulate mRNA levels of TLR negative regulators and protein levels of p38 MAPK and p65 NF-κB transcription factors. However, these modulations were differed remarkably between both free fatty acid treated and untreated HepG2 cells. Heat-killed LABs were also indirectly suppressed THP-1 cells to produce higher level of IL-10, TLR4, and lower at genes level of TGF-β, IL-1β, and IL-6, and at protein level of TNF-α in response to LPS. Taken together, our findings indicate that selected LABs exhibit profound immunoregulatory effects on liver cells via modulation of TLR negative regulators of the MAPK and NF-κB pathways.

Highlights

Inflammation plays a pivotal role in disease and health, and is a prime immune response triggered by injury to living tissues
A p < 0.05 was considered to indicate statistical significance. Lactic acid bacteria, such as L. plantarum DU1, L. farciminis, W. cibaria DU1, and L. pentosus were isolated from fermented foods and characterized phenotypically and genotypically
We demonstrated that Total cellular fluid (TCF) of LAB strains reduced the accumulation of lipid and modulated the inflammatory response induced by LPS in hepatoma HepG2 cells

Summary

Introduction

Inflammation plays a pivotal role in disease and health, and is a prime immune response triggered by injury to living tissues. The inflammatory response is a protective mechanism that evolved in living things to protect against injury, infection, trauma, and noxious stimuli [1]. The purpose of this process is to eliminate injurious agents or intruders and to clear the components of damaged tissues. Probiotics Attenuates Hepatoma Cell Inflammation factors can induce inflammation, microbes and their cellular components are considered to be the most common cause of inflammatory response in the host [2]. Lipopolysaccharide (LPS) is a major cellular component of Gram-negative bacteria, which is able to induce pro-inflammatory pathways leading to an inflammation and progression of several disease, including alcoholic and nonalcoholic liver diseases [3,4,5]. During the gut barrier disruption, LPS migrates from the intestinal lumen to other extra-intestinal body organs including liver via the portal vein, where it activates hepatic and extra hepatic macrophages to produce reactive oxygen species and pro-inflammatory cytokines/ chemokines, such as IL-1, IL-6, IL-8, and TNF-α, resulting in liver inflammation [3, 5]

Methods

Results

Conclusion