Emilie Merour

Publications of Emilie Merour

• Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon.

  Authors: Laurent Peyrin-Biroulet, Julia Beisner, Guoxing Wang, Sabine Nuding, Sajit Thottathil Oommen, Denise Kelly, Erika Parmentier-Decrucq, Rodrigue Dessein, Emilie Merour, Philipe Chavatte, Teddy Grandjean, Aude Bressenot, Pierre Desreumaux, Jean-Frédéric Colombel, Béatrice Desvergne, Eduard F Stange, Jan Wehkamp, Mathias Chamaillard

  Proceedings of the National Academy of Sciences of the United States of America. 05/2010; 107(19):8772-7.

  Crohn's disease (CD), a major form of human inflammatory bowel disease, is characterized by primary immunodeficiencies. The nuclear receptor peroxisome proliferator-activated receptor gammaCrohn's disease (CD), a major form of human inflammatory bowel disease, is characterized by primary immunodeficiencies. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is essential for intestinal homeostasis in response to both dietary- and microbiota-derived signals. Its role in host defense remains unknown, however. We show that PPARgamma functions as an antimicrobial factor by maintaining constitutive epithelial expression of a subset of beta-defensin in the colon, which includes mDefB10 in mice and DEFB1 in humans. Colonic mucosa of Ppargamma mutant animals shows defective killing of several major components of the intestinal microbiota, including Candida albicans, Bacteroides fragilis, Enterococcus faecalis, and Escherichia coli. Neutralization of the colicidal activity using an anti-mDefB10 blocking antibody was effective in a PPARgamma-dependent manner. A functional promoter variant that is required for DEFB1 expression confers strong protection against Crohn's colitis and ileocolitis (odds ratio, 0.559; P = 0.018). Consistently, colonic involvement in CD is specifically linked to reduced expression of DEFB1 independent of inflammation. These findings support the development of PPARgamma-targeting therapeutic and/or nutritional approaches to prevent colonic inflammation by restoring antimicrobial immunity in CD.

• Hepatitis C virus (HCV) proteins induce lipogenesis and defective triglyceride secretion in transgenic mice.

  Authors: Herve Lerat, Helene L Kammoun, Isabelle Hainault, Emilie Merour, Martin R Higgs, Celine Callens, Stanley M Lemon, Fabienne Foufelle, Jean-Michel Pawlotsky

  The Journal of biological chemistry. 10/2009;

  Chronic hepatitis C virus (HCV) infection is associated with altered lipid metabolism and hepatocellular steatosis. Virus-induced steatosis is a cytopathic effect of HCV replication. The goal of thisChronic hepatitis C virus (HCV) infection is associated with altered lipid metabolism and hepatocellular steatosis. Virus-induced steatosis is a cytopathic effect of HCV replication. The goal of this study was to examine the mechanisms underlying HCV-induced lipid metabolic defects in a transgenic mouse model expressing the full HCV protein repertoire at levels corresponding to natural human infection. In this model, expression of the HCV full-length open reading frame was associated with hepatocellular steatosis and reduced plasma triglyceride levels. Triglyceride secretion was impaired, whilst lipogenesis was activated. Increased lipogenic enzyme transcription was observed, resulting from maturational activation and nuclear translocation of sterol regulatory element binding protein 1c (SREBP1c). However, ER-stress markers were expressed at similar levels in both HCV transgenic mice and their wild-type counterparts, suggesting that SREBP1c proteolytic cleavage in the presence of HCV proteins was independent of ER stress. In conclusion, transgenic mice expressing the HCV full-length polyprotein at low levels have decreased plasma triglyceride levels and develop hepatocellular steatosis in the same way as HCV-infected patients. In these mice, SREBP1c activation by one or several HCV proteins induces de novo triglyceride synthesis via the lipogenic pathway, in a manner independent of ER stress, whilst triglyceride secretion is simultaneously reduced.

• Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors.

  Authors: Christel Rousseaux, Xavier Thuru, Agathe Gelot, Nicolas Barnich, Christel Neut, Laurent Dubuquoy, Caroline Dubuquoy, Emilie Merour, Karen Geboes, Mathias Chamaillard, Arthur Ouwehand, Greg Leyer, Didier Carcano, Jean-Frédéric Colombel, Denis Ardid, Pierre Desreumaux

  Nature medicine. 02/2007; 13(1):35-7.

  Abdominal pain is common in the general population and, in patients with irritable bowel syndrome, is attributed to visceral hypersensitivity. We found that oral administration of specificAbdominal pain is common in the general population and, in patients with irritable bowel syndrome, is attributed to visceral hypersensitivity. We found that oral administration of specific Lactobacillus strains induced the expression of mu-opioid and cannabinoid receptors in intestinal epithelial cells, and mediated analgesic functions in the gut-similar to the effects of morphine. These results suggest that the microbiology of the intestinal tract influences our visceral perception, and suggest new approaches for the treatment of abdominal pain and irritable bowel syndrome.