Lactobacillus casei MYL01 modulates the proinflammatory state induced by ethanol in an in vitro model.
Accumulating studies have suggested that probiotics have beneficial effects on liver injury but the underlying mechanism has remained unclear. Toll-like receptors (TLR) expressed on immune cells and hepatocytes recognize bacterial components that are translocated from the gut into the portal vein. To date, it has been demonstrated that ethanol alone, without microbial components, is able to activate TLR, leading to promotion of proinflammatory cytokine production. Because the enhanced signaling of TLR triggers persistent inflammation, we hypothesized that development of hepatocyte TLR tolerance to repetitive stimulation plays an important role in protecting the liver from hypergeneration of proinflammatory cytokines. In this study, we showed that Lactobacillus casei MYL01 modulated the proinflammatory state induced by ethanol and investigated in detail the mechanism underlying the observation that L. casei MYL01 gave rise to TLR tolerance toward ethanol stimulation. The effects of L. casei MYL01 in the attenuation of ethanol-induced liver damage were due to enhancement of IL-10 production, which limited the proinflammatory process. Furthermore, better defense of hepatocytes against ethanol challenge by treatment of L. casei MYL01 was attributed to previous induction of toll interacting protein (TOLLIP) and suppressor of cytokine signaling (SOCS)1 and SOCS3 expression via activation of TLR1, TLR2, TLR6, and TLR9, an action that cross-regulated ethanol-TLR4-nuclear factor κB signal transduction events. This finding might help establish an in vitro platform for selecting hepatoprotective probiotic strains in terms of ethanol-induced liver damage.
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan, Republic of China.
Yi-Heng
YH
Chiu
Department of Internal Medicine, Veterans General Hospital International Medical Service Centre, Taichung 40705, Republic of China.
Jaw-Ji
JJ
Tsai
Department of Neurology, Chong Guang Hospital, Miaoli County 35159, Taiwan, Republic of China.
Shiao-Lin
SL
Lin
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan, Republic of China. Electronic address: meeiynlin@gmail.com.
Meei-Yn
MY
Lin
D000431:Ethanol / Q000009:adverse effects*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000382:microbiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000382:microbiology; D016753:Interleukin-10 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D019936:Probiotics / Q000494:pharmacology; D034622:RNA Interference; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; C495371:TLR9 protein, human; C410602:TOLLIP protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D016753:Interleukin-10; D000431:Ethanol
ethanol; liver injury; probiotic; toll-like receptor