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Bacteria biofilms regulate human cathelicidin transcription in the gut through VDR signaling
Author(s) -
RestaLenert Silvia Cristina,
Lee Susan J,
Azarenok Serge,
Maruggi Marco
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1182.7
Subject(s) - calcitriol receptor , cathelicidin , biology , microbiology and biotechnology , innate immune system , immune system , receptor , immunology , biochemistry
Antimicrobial cathelicidins, are produced by mucosal cells in innate and adaptive immunity. Crohn's disease (CD) is characterized by low levels of cathelicidins and vit.D receptor (VDR). VDR activation stimulates LL‐37 synthesis. Moreover, certain enteric bacteria are prevalent in the gut of patients with CD. We showed that commensals and probiotics regulate VDR and calcium metabolism in chronic inflammation. We hypothesized that low cathelicidins levels in CD results from inhibition of VDR signaling by enteroadhesive bacteria and that this can be prevented by probiotics. Enteroadhesive E.coli (EADEC from a CD case), and probiotics (S.thermophilus, ST, and L.acidophilus, LA) were grown as biofilms. Caco‐2 and HT29/cl 19A cells were grown as monolayers and treated for 24‐48 hr with/without EADEC and ST/LA. IL‐10 −/− and WT mice were treated with ST/LA for 4 wk in vivo. Cells, and small intestinal (SMI) and colonic tissues (CT) were examined for VDR and cathelicidin (LL‐37 and mCRAMP) by mRNA and protein analysis. A significant reduction of VDR and cathelicidins (3‐ and 5‐fold vs. controls for cells and tissues, respectively) was found in EADEC‐treated cells and in colitic tissues. This was reversed by probiotics. Moreover, a VDR siRNA blocked the effect of probiotics in EADEC‐primed cells. Similarly, lower mCRAMP was observed in ex vivo cultures of SMI and CT treated with an inactive vit. D analog. Our data underscore the role of the gut microbiota in regulating physiologic functions of the host and suggest that complex pathways are activated by probiotic and commensal bacteria. Supported by grants NIH‐DK062096 and UCSD Academic Senate (SRL)