Prostaglandins I2 and E2 have a synergistic role in rescuing epithelial barrier function in porcine ileum.

Abstract

Prostaglandins (PG) are cytoprotective for gastrointestinal epithelium, possibly because they enhance mucosal repair. The objective of the present studies was to assess the role of prostaglandins in intestinal repair. Intestinal mucosa from porcine ileum subjected to 1 h of ischemia was mounted in Ussing chambers. Recovery of normal transepithelial electrical resistance occurred within 2 h, and continued to increase for a further 2 h to a value twice that of control. The latter response was blocked by inhibition of prostaglandin synthesis, and restored by addition of both carbacyclin (an analog of PGI 2 ) and PGE 2 , whereas the addition of each alone had little effect. Histologically, prostaglandins had no effect on epithelial restitution or villous contraction, indicating that elevations in transepithelial resistance were associated with increases in paracellular resistance. Furthermore, prostaglandin-stimulated elevations in resistance were inhibited with cytochalasin D, an agent known to stimulate cytoskeletal contraction. Synergistic elevations in transepithelial resistance, similar to those of carbacyclin and PGE 2 , were also noted after treatment with cAMP and A23187 (a calcium ionophore). We conclude that PGE 2 and PGI 2 have a synergistic role in restoration of intestinal barrier function by increasing intracellular cAMP and Ca 2 ϩ , respectively, which in turn signal cytoskeletal-mediated tight junction closure. ( J. Clin. Invest. 1997Invest. . 100:1928Invest. -1933

Prophylactic Effect of Rebamipide on Aspirin-Induced Gastric Lesions and Disruption of Tight Junctional Protein Zonula Occludens-1 Distribution

“…These results indicate that rebamipide also exhibited the protective effect on aspirin-induced gastric lesions via keeping tight junctional complexes. Although the mechanism of rebamipide to keep distribution of ZO-1 protein was not clarified in this study, Blikslager et al reported that prostaglandins played an important role in keeping the barrier function by increasing intracellular cAMP and Ca 2+ (67). In fact, Suestugu et al reported (68) that rebamipide increased the cAMP production when it was co-cultured with prostaglandin E 2 in RGM-1 cells, although rebamipide itself did not increase cAMPproduction.…”

A report of left dorsal displacement of the large colon in a tropical horse

“…Probability of survival can be influenced by loss of the epithelial barrier, which allows transmucosal leakage of endotoxin, bacterial chemotactic peptides, and bacteria [13] . Rapid repair of the epithelium is important for recovery and involves 2 processes that are usually completed within hours: mucosal restitution and tightening of paracellular pathways between remaining cells [20,21] . Restitution involves sealing the mucosal defect with remaining viable cells before final repair through cell division and proliferation [22] .…”

Roles of Myofibroblasts in Prostaglandin E2–Stimulated Intestinal Epithelial Proliferation and Angiogenesis

“…Short-term administration of PGE 2 causes significant stimulation of DNA synthesis; prolonged PGE 2 treatment markedly increases the weight and DNA content of the intestinal mucosa (4). PGE 2 and prostacyclin stimulate intestinal epithelial cell migration and therefore promote intestinal restitution (5). Moreover, PGE 2 exerts growth-stimulatory effects on intestinal tumors, and administration of PGE 2 provides a growth advantage to intestinal neoplasms (6,7).…”