title: Lactobacillus paracasei Induces M2-Dominant Kupffer Cell Polarization in a Mouse Model of Nonalcoholic Steatohepatitis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Lactobacillus paracasei attenuates hepatic steatosis with M2-dominant Kupffer cell polarization in a NASH model.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Sohn
authors.affiliation: Department of Internal Medicine, Hanyang University School of Medicine, 17 Haengdang-dong Sungdong-gu, Seoul, 133-792, Korea. noshin@hanyang.ac.kr.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Jun
authors.affiliation: Department of Internal Medicine, Hanyang University School of Medicine, 17 Haengdang-dong Sungdong-gu, Seoul, 133-792, Korea.
authors.forename: Kang Nyeong
authors.initials: KN
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hanyang University School of Medicine, 17 Haengdang-dong Sungdong-gu, Seoul, 133-792, Korea.
authors.forename: Hang Lak
authors.initials: HL
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hanyang University School of Medicine, 17 Haengdang-dong Sungdong-gu, Seoul, 133-792, Korea.
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hanyang University School of Medicine, 17 Haengdang-dong Sungdong-gu, Seoul, 133-792, Korea.
authors.forename: Ho Soon
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Hanyang University School of Medicine, 17 Haengdang-dong Sungdong-gu, Seoul, 133-792, Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoon
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D007778:Lactobacillus / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000628:therapy*; D010539:Permeability; D010641:Phenotype; D019936:Probiotics; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins
keywords: Kupffer cells; Lactobacillus; Nonalcoholic steatohepatitis; Probiotics