DICAM Attenuates Experimental Colitis via Stabilizing Junctional Complex in Mucosal Barrier.

Background: Adhesion molecules maintain the intestinal barrier function that is crucial to prevent intestinal inflammation. Dual immunoglobulin domain-containing adhesion molecule (DICAM) has been recently identified and known for the involvement in cell-cell adhesion through homophilic interaction and heterophilic interaction with integrin αVβ3. We tested whether the change of DICAM expression affects the severity of colonic inflammation.

Methods: Colitis was induced with oral administration of 2.5% dextran sulfate sodium (DSS) in 8-week-old male mice for 5 days. The function of DICAM under inflammatory condition was investigated using loss-of-function and gain-of-function models such as DICAM-deficient mice and adenoviral transduction of DICAM into Caco-2 colonic epithelial cells.

Results: DICAM increased in parallel with the degree of inflammation after 5-day administration of DSS and decreased with the resolution of inflammation. DICAM was expressed in the epithelial junctional complex and colocalized with ZO-1. Treatment with TNF-α or IFN-γ in Caco-2 cells significantly increased DICAM in protein and RNA level. The DICAM knockout mice showed more severe DSS-induced colitis compared with WT littermates. Adenoviral transduction of DICAM into Caco-2 cells significantly attenuated the inflammation-mediated decrease of adhesion molecules, including ZO-1 and occludin. Furthermore, Caco-2 cells with DICAM overexpression maintained intestinal barrier function under IFN-γ treatment as estimated by transepithelial electrical resistance.

Conclusion: Our study demonstrates that DICAM which is increased in an inflammatory condition has a protective role in experimental colitis by stabilizing the integrity of junctional complex in the intestinal mucosal barrier.