This review shows an overview of the genetic and environmental factors that appear to influence both the occurrence of IBD and CRC with particular reference to <i>NOD2</i> and <i>TLRs</i> as well as pro- and anti-inflammatory cytokines associated with tumor initiation and progression (encompassing both tumor invasion and metastases), as they constitute potential targets for therapeutic intervention.
Use of WFA demonstrated that vimentin was required for NOD2-dependent NF-κB activation and muramyl dipeptide-induced autophagy induction, and that NOD2 and vimentin regulated the invasion and survival properties of a CD-associated adherent-invasive Escherichia coli strain.
Our results demonstrated that Nod2 recruits the critical autophagy protein ATG16L1 to the plasma membrane during bacterial invasion and that cells expressing mutations in these proteins--two of the most important associated with Crohn disease--autophagy is defective upon infection or stimulation with the bacterial peptidoglycan fragment MDP.
The most admitted hypothesis suggests that the impaired function of Nod2 variants in intestinal epithelial and phagocytic cells results in deficiencies in epithelial-barrier function which subsequently lead to increased bacterial invasion and inflammation at intestinal sites.
Expression of TNF-alpha mRNA was enhanced following bacterial invasion in all cell lines but NOD2(Blau) was associated with a more rapid decline in TNF-alpha expression.
CARD15 is involved in the recognition of bacterial peptidoglycan-derived muramyl dipeptide (MDP) and will stimulate secretion of antimicrobial peptides including alpha-defensins (also called cryptdins) to protect the host from invasion.