In contrast, PBMCs from a patient homozygous for the Nod2 R702W mutation, also associated with Crohn disease, displayed normal response to Gram-negative bacterial peptidoglycan.
SAM also detected altered ileal gene expression in unaffected NOD2(NR) ileal mucosal CD samples compared to NOD2(NR) control samples. qRT-PCR conducted on all the samples confirmed that increased CD3D expression in affected samples was associated with NOD2(R) status, and that increased MUC1, DUOX2, DMBT1 and decreased C4orf7 expression in unaffected samples was associated with CD, independent of NOD2 status.
The cells also strongly and specifically express the NOD2 gene product, one of an emerging family of critical, intracellular mediators of innate immune responses, which is also highly expressed in peripheral blood mononuclear cells, and they express RNA for tumor necrosis factor alpha, a major myelomonocytic cell-derived cytokine, which has a crucial role in the pathogenesis of diseases such as rheumatoid arthritis and Crohn's disease (CD).
Expression of mouse Nod2 activated NF-kappaB and conferred responsiveness to bacterial components, an activity that was deficient in mutants corresponding to those associated with susceptibility to Crohn's disease.
Patients with CD in clinical remission or with very low disease activity according to the Crohn's disease activity index were genotyped regarding nucleotide-binding oligomerization domain 2 (<i>NOD2</i>), and PBMCs from wild-type (WT)-<i>NOD2</i> patients, patients with homozygous or heterozygous <i>NOD2</i> mutations and healthy donors were isolated for further analysis.
Thus, NOD2 mediates the host response to bacterial muropeptides derived from peptidoglycan, an activity that is important for protection against Crohn's disease.
Since NOD2 is over-expressed in CD and mutant NOD2cannot result in NF-κB activity, our finding can provide an explanation of the previous observation showing decreased expression of human enteric α-defensin in CD and even more so in the presence of NOD2 mutations.
In context with an increased expression of IL-18 in CD, it remains to be shown whether the expression of IL-18 is influenced by CARD15/NOD2 mutation status.
To address the hypothesis that the function of NOD2 may affect expression of Paneth cell defensins, we compared their expression levels with respect to NOD2 mutations in Crohn's disease.
DCs from individuals with Crohn's disease expressing Crohn's disease-associated NOD2 or ATG16L1 risk variants are defective in autophagy induction, bacterial trafficking and antigen presentation.
Reduction in alpha-defensin expression is independent of NOD2 status and is due to loss of surface epithelium as a consequence of inflammatory changes rather than being the inciting event prior to inflammation in ileal Crohn's disease.
Reduction in alpha-defensin expression is independent of NOD2 status and is due to loss of surface epithelium as a consequence of inflammatory changes rather than being the inciting event prior to inflammation in ileal Crohn's disease.
CD-associated polymorphisms affected the elimination of MAP from ex vivo monocytes (NOD2), or expression of certain cytokines (ATG16L1), implying independent but contributory roles in the pathogenesis of CD.
Hydrodynamic procedure efficiently delivers the IL10 gene to the human colon, achieving levels of tissue protein expression high enough to mediate pharmacological effects with interest in controlling immune response in patients with Crohn's disease.
Intracellular IL-10 expression by CD4<sup>+</sup> T-cell subsets in the inflamed guts of patients with IBD (Crohn disease or ulcerative colitis) was compared with that in cells from noninflamed control subjects.
ATG16L1 and LC3 expression was analyzed in the inflamed ileum and colon of 28 patients with Crohn's disease (CD), 14 with ulcerative colitis (UC) and 23 controls by western blot.
The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD.
We investigated two hypotheses: (1) that oral inoculation of Il10-/- mice would result in greater and more consistent intestinal inflammation than that observed in Il10-/- mice not receiving this inoculation, and (2) that this inflammation would be associated with changes in colon gene expression levels similar to those previously observed in human studies, and these mice would therefore be an appropriate model for human CD.