Cross-talk between intestinal epithelial cells and immune cells in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) involves functional impairment of intestinal epithelial cells (IECs), concomitant with the infiltration of the lamina propria by inflammatory cells. We explored the reciprocal paracrine and direct interaction between human IECs and macrophages (MΦ) in a co-culture system that mimics some aspects of IBD. We investigated the expression of intercellular junctional proteins in cultured IECs under inflammatory conditions and in tissues from IBD patients. IECs establish functional gap junctions with IECs and MΦ, respectively. Connexin (Cx26) and Cx43 expression in cultured IECs is augmented under inflammatory conditions; while, Cx43-associated junctional complexes partners, E-cadherin, ZO-1, and β-catenin expression is decreased. The expression of Cx26 and Cx43 in IBD tissues is redistributed to the basal membrane of IEC, which is associated with decrease in junctional complex proteins’ expression, collagen type IV expression and infiltration of MΦ. These data support the notion that the combination of paracrine and hetero-cellular communication between IECs and MΦs may regulate epithelial cell function through the establishment of junctional complexes between inflammatory cells and IECs, which ultimately contribute to the dys-regulation of intestinal epithelial barrier.

Immunomodulatory properties of Olea europaea leaf extract in intestinal inflammation

“…3). Moreover, it has been reported that the increased expression and/or production of different inflammatory cytokines can facilitate the breaking of the intestinal subepithelial basement membrane, and thus promote the presence of activated mononuclear cells in close proximity to the intestinal epithelial cells [25]. Such situation may lead to the disruption of junctional complexes in the mucosal epithelium, as evidenced in the present study, by the decrease in the expression of ZO-1 (zonula occludens) and/or TFF-3 (trefoil factor) in the experimental models of colitis ( Figs.…”

Cytoplasmic Form of Carlr lncRNA Facilitates Inflammatory Gene Expression upon NF-κB Activation

“…To evaluate the role of Carlr in the macrophage-enterocyte interaction, we assessed the localization of Carlr in the intestinal cell line Caco2 at steady state and in the presence of LPS and activated THP-1 cells. This cell line is widely used as a model for human intestinal inflammatory diseases and is able to produce NF-κB regulated cytokines such as IL-6 (24–26). Caco2 cells showed nuclear localization of Carlr at basal conditions, however, when co-culturing the intestinal cells with LPS or with activated THP-1 cells, resembling the intestinal inflammatory environment, we saw that Carlr expression was increased and at the same time translocated to the cytoplasm, mainly in the co-culture condition (Figure 3D).…”

The function of macromolecular complex of CFTR-NHERF2-LPA2 in inflammatory responses of intestinal epithelial cells

“…The characterization of alterations in tight junction proteins are key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. The disruption of integrity of the epithelial barrier may intrigue the onset of inflammatory bowel diseases[15]. The leaky intestinal epithelial barrier is mainly attributed to defects of the TJs and IEC loss[14]; the deficient TJs are the primary cause for the compromised intestinal epithelial barrier[3].…”