Sera from patients with Crohn's disease break bacterial lipopolysaccharide tolerance of human intestinal epithelial cells via MD-2 activity.
Myeloid differentiation (MD)-2 is linked to the cell surface as a Toll-like receptor (TLR) 4-bound protein though may also function as a soluble receptor to enable the lipopolysaccharide (LPS)-driven response. We recently demonstrated the importance of MD-2 either as a cell-associated or as a soluble receptor in the control of intestinal epithelial cell response toward LPS. High levels of circulating MD-2 were recently proposed as a risk factor for infectious/ inflammatory diseases as septic shock. We hypothesized that MD-2 might be present in sera from patients with inflammatory bowel disease and have pathogenic consequences. We analysed MD-2 activity in sera from patients with inflammatory bowel disease or from healthy subjects. We measured MD-2 activity as the capacity to mediate LPS-driven stimulation of intestinal epithelial cells (HT29). We found that sera from patients with inflammatory bowel disease, particularly Crohn's disease, endowed HT29 cells with a markedly higher LPS-dependent stimulating capacity as compared to sera from healthy subjects. The effect of sera was specific for LPS activation and was reduced in the presence of anti-MD-2, and anti-TLR4 antibodies. We conclude that sera from patients with inflammatory bowel disease might contain increased MD-2. This might result in higher local availability of the protein leading to a loss of tolerance toward gut microbiota.
Seksik
Philippe
P
ER7-UPMC, University of Paris 6, Paris, France.
Sokol
Harry
H
Grondin
Virginie
V
Adrie
Christophe
C
Duboc
Henri
H
Pigneur
Benedicte
B
Thomas
Ginette
G
Beaugerie
Laurent
L
Trugnan
Germain
G
Masliah
Joelle
J
Bachelet
Maria
M
D000328:Adult; D003093:Colitis, Ulcerative / Q000097:blood* / Q000276:immunology; D003424:Crohn Disease / Q000097:blood* / Q000276:immunology; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051218:Lymphocyte Antigen 96 / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged
C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96