Regulation of CEACAM Family Members by IBD-Associated Triggers in Intestinal Epithelial Cells, Their Correlation to Inflammation and Relevance to IBD Pathogenesis.

Carcinoembryogenic antigen cellular adhesion molecules (CEACAMs) are intercellular adhesion molecules highly expressed in intestinal epithelial cells. CEACAM1, -3, -5, -6, -7 are altered in patients suffering from colon cancer and inflammatory bowel diseases (IBD), but their role in the onset and pathogenesis of IBD is not well known. Herein, we aim to correlate CEACAM1, -3, -5, -6, -7 expression to the degree of inflammation in pediatric and adult IBD colon biopsies and to examine the regulation of CEACAMs on human intestinal epithelial cell lines (C2BBe1/HT29) by different IBD-associated triggers (cytokines, bacteria/metabolites, emulsifiers) and IBD-drugs (6-Mercaptopurine, Prednisolone, Tofacitinib). Biopsies from patients with pediatric Crohn's disease (CD) and adult ulcerative colitis (UC, active/inactive disease) showed a significant increase in CEACAM3, -5, -6 expression, while CEACAM5 expression was reduced in adult CD patients (active/inactive disease). Intestinal epithelial cells cultured with a pro-inflammatory cytokine cocktail and Adherent-invasive Escherichia coli (AIEC) showed a rapid induction of CEACAM1, -5, -7 followed by a reduced RNA and protein expression overtime and a constant expression of CEACAM3, correlating with IL-8 expression. Cells cultured with the emulsifier polysorbate-80 resulted in a significant induction of CEACAM3, -5, -6, -7 at a late time point, while SCFA treatment reduced CEACAM1, -5, -7 expression. No major alterations in expression of CEACAMs were noted on cells cultured with the commensal Escherichia coli K12 or the pathogen Salmonella typhimurium. IBD drugs, particularly Tofacitinib, significantly reduced cytokine-induced CEACAM1, -3, -5, -6, -7 expression associated with a reduced IL-8 secretion. In conclusion, we provide new evidence on the regulation of CEACAMs by different IBD-associated triggers, identifying a role of CEACAMs in IBD pathogenesis.

Carcinoembryonic antigen (CEACAM) family members and Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic intestinal inflammatory condition with increasing incidence worldwide and whose pathogenesis remains largely unknown. The collected evidence indicates that genetic, environmental and microbial factors and a dysregulated immune response are responsible for the disease. IBD has an early onset and long term sufferers present a higher risk of developing colitis associated cancer (CAC). The carcinoembryonic antigen-related adhesion molecules (CEACAM) are a subgroup of the CEA family, found in a range of different cell types and organs including epithelial cells in the intestine. They can act as intercellular adhesions molecules for e.g. bacteria and soluble antigens. CEACAMs are involved in a number of different processes including cell adhesion, proliferation, differentiation and tumour suppression. Some CEACAMs such as CEACAM1, CEACAM5 and CEACAM6 are highly associated with cancer and are even recognised as valid clinical markers for certain cancer forms. However, their role in IBD pathogenesis is less understood. The purpose of this review is to provide a comprehensive summary of published literature on CEACAMs and intestinal inflammation (IBD). The interactions between CEACAMs and bacteria adhesion in relation to IBD pathophysiology will be addressed and potential new therapeutic and diagnostic opportunities will be identified.