P030 - ENPP1 EXPRESSION IN GUT MUCOSAL EPITHELIA INFLUENCES BARRIER FUNCTION VIA THE ADENOSINE PATHWAY
(Room Poster Hall)
19 Jan 18
5:30 PM
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7:00 PM
Tracks:
Clinical and Research Challenges
Previous work has established that extracellular adenosine signaling is protective in mucosal inflammation and promotes the resolution of ongoing inflammation. The sources of extracellular adenosine include enzymatic processing from nucleotides, such as ATP, AMP, and diadenosine triphosphate (Ap3A), which can be liberated from a variety of cell types, including leukocytes. Here, we revealed that activated human neutrophils are a source of Ap3A, previously thought to be made primarily by platelets. Certain members of the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) family can process such nucleotides, representing additional apyrases that may be expressed on intestinal epithelial cells. ENPP1, a type II transmembrane glycoprotein that can hydrolyze ATP and Ap3A and is present on the surface of chondrocytes, has been extensively studied for its role in tissue mineralization. Its potential role in the resolution of mucosal inflammation via AMP generation has not previously been described. Presently, we have established that ENPP1 mRNA is expressed in T84 intestinal epithelial cells, and knockdown of this expression impairs barrier function and migration ability. Alternatively, overexpression of ENPP1 enhances barrier formation and improves wound healing. These studies indicate that Ap3A and ENPP1 present on intestinal epithelial cells may function to provide an additional source of adenosine, sub-serving its role in inflammatory resolution.