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- Title
Lactobacillus paracasei Induces M2-Dominant Kupffer Cell Polarization in a Mouse Model of Nonalcoholic Steatohepatitis.
- Authors
Sohn, Won; Jun, Dae; Lee, Kang; Lee, Hang; Lee, Oh; Choi, Ho; Yoon, Byung; Jun, Dae Won; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Choi, Ho Soon; Yoon, Byung Chul
- Abstract
<bold>Background and Aims: </bold>Gut microbiota may be associated with the pathogenesis of nonalcoholic steatohepatitis (NASH). This study aimed to investigate the protective effects and possible mechanisms of Lactobacillus paracasei on NASH.<bold>Methods: </bold>Thirty male C57BL/6 mice were randomized into three groups and maintained for 10 weeks: control group (standard chow), NASH model group (high fat + 10 % fructose diet), and the L. paracasei group (NASH model with L. paracasei). Liver histology, serum aminotransferase levels, and hepatic gene expression levels were measured. Intestinal permeability was investigated using urinary (51)Creatinine Ethylenediaminetetraacetic acid ((51)Cr-EDTA) clearance. Total Kupffer cell counts and their composition (M1 vs. M2 Kupffer cells) were measured using flow cytometry with F4/80 and CD206 antibodies.<bold>Results: </bold>Hepatic fat deposition, serum ALT level, and (51)Cr-EDTA clearance were significantly lower in the L. paracasei group than the NASH group (p < 0.05). The L. paracasei group had lower expression in Toll-like receptor-4 (TLR-4), NADPH oxidase-4 (NOX-4), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin 4 (IL-4), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-δ compared with the NASH group (p < 0.05). The total number of F4/80(+) Kupffer cells was lower in the L. paracasei group than the NASH group. L. paracasei induced the fraction of F4/80(+)CD206(+) cells (M2 Kupffer cells) while F4/80(+)CD206(-) cells (M1 Kupffer cells) were higher in the NASH group (F4/80(+)CD206(+) cell: 44% in NASH model group vs. 62% in L. paracasei group, p < 0.05).<bold>Conclusions: </bold>Lactobacillus paracasei attenuates hepatic steatosis with M2-dominant Kupffer cell polarization in a NASH model.
- Subjects
THERAPEUTICS; GUT microbiome; LACTOBACILLUS; ANIMAL experimentation; BIOLOGICAL models; CELLULAR signal transduction; FATTY liver; INFLAMMATORY mediators; INTESTINES; MACROPHAGES; MICE; PERMEABILITY; TIME; PHENOTYPES; PROBIOTICS; SIGNAL peptides; PHYSIOLOGY
- Publication
Digestive Diseases & Sciences, 2015, Vol 60, Issue 11, p3340
- ISSN
0163-2116
- Publication type
journal article
- DOI
10.1007/s10620-015-3770-1