Inflammatory bowel disease is associated with changes of enterocytic junctions

Abstract

Changes of the intestinal mucosal barrier are considered to play a role in the pathogenesis of inflammatory bowel disease (IBD). Our experiments were designed to identify dysregulation of epithelial junctional molecules in the IBD intestinum and to address whether altered expression of these molecules is a primary event in IBD or a phenomenon secondary to the inflammatory process. Noninflamed and inactively and actively inflamed mucosal tissues from patients with ulcerative colitis or Crohn's disease as well as tissues from control subjects were analyzed for the expression of junctional molecules by different methods. Marked downregulation of junctional proteins and their respective mRNAs was observed in actively inflamed IBD tissues. In IBD tissues with inactive inflammation, only a few junctional molecules such as E-cadherin and α-catenin were affected, whereas expression of desmosomal or tight junction-associated proteins appeared almost unchanged. In noninflamed IBD tissues, junctional protein expression was not different from that seen in normal control subjects. In IBD, downregulation of junctional molecule expression is apparently associated with the inflammatory process and does not likely represent a primary phenomenon.

Optimal dietary protein level improved growth, disease resistance, intestinal immune and physical barrier function of young grass carp (Ctenopharyngodon idella)

“…Here, the altered ZO-1 (rather than ZO-2) mRNA levels that resulted from dietary proteins might be partly related to inflammation. Gassler et al [80] reported that in human intestinal inflamed mucosal tissues, ZO-1 gene expression was down-regulated, while the gene expression of ZO-2 was unaltered. This study found that low or high levels of protein triggered intestinal inflammation in young grass carp after infection with A. hydrophila.…”

Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells

“…25 Junctional proteins show reduced expression or changes in distribution in gut inflammation. [26][27][28] The dynamic nature of tight junctions is well demonstrated by the ability of cytokines and growth factors to modulate tight junction protein expression, regulate junction assembly and change epithelial permeability. [29][30][31][32][33] It has been established for many years that the cytokine profile of CD is T-helper type 1 and shows increased expression of the cytokines, TNFa and IFNg.…”

Current view of the immunopathogenesis in inflammatory bowel disease and its implications for therapy

“…The intestinal epithelium is considered a constitutive component of the mucosal immune system. Intestinal epithelial cells (IECs) are connected by tight junctions, which are dynamically regulated in response to cytokines and are down-regulated by the junctional complexes in human IBD (E-cadherin and β-catenin) [38] . The epithelium is in constant communication with luminal flora and the underlying network of innate and adaptive immune cells, and IECs constitutively express or can be induced to express costimulatory molecules [39] and components of the human major histocompatibility complex (MHC) [40] , toll-like receptors (TLRs) [41] , NOD proteins [42] , inflammatory cytokines [43] , as well as antimicrobial peptides [44] .…”