16-16-dimethylprostaglandin-e2 and Inflammation

The effect of potential mediators of mucus secretion was investigated in the isolated vascularly perfused rat colon by using a sandwich enzyme-linked immunosorbent assay for rat colonic mucin and by histochemical analysis. Bethanechol (100-200 microM), bombesin (100 nM), and vasoactive intestinal peptide (VIP, 100 nM) provoked a dramatic mucin discharge (maximal response at 900, 900, and 600% of control loops, respectively). VIP-stimulated mucin secretion was abolished by tetrodotoxin, whereas atropine was without effect. In contrast, both tetrodotoxin and atropine significantly decreased mucin release induced by bombesin. Isoproterenol or calcitonin gene-related peptide was without effect. Serotonin (1-5 microM) and peptide YY (10 nM) evoked mucin discharge, whereas glucagon-like peptide-1 did not release mucin. Finally, bromolasalocid (20 microM), interleukin-1beta (0.25 nM), sodium nitroprusside (1 mM), and dimethyl-PGE2 (2.5 microM) induced mucus discharge. The results demonstrated a good correlation between the immunological method and histological analysis. In conclusion, these findings suggest a role for the enteric nervous system, the enteroendocrine cells, and resident immune cells in mediation of colonic mucus release.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Atropine; Bethanechol; Bombesin; Calcitonin Gene-Related Peptide; Colon; Enteric Nervous System; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Inflammation; Interleukin-1; Intestinal Mucosa; Isoproterenol; Lasalocid; Male; Mucus; Neurotransmitter Agents; Nitroprusside; Peptide Fragments; Peptide YY; Protein Precursors; Rats; Rats, Wistar; Serotonin; Tetrodotoxin; Vasoactive Intestinal Peptide

We studied the effects of the oral administration of a stable prostaglandin E2 analog, 16,16-dimethyl prostaglandin E2, on the intrahepatic biliary branches in a canine model. Obstructive cholestasis with a bacterial infection was induced surgically in two liver lobes in healthy mongrel dogs, and 16,16-dimethyl prostaglandin E2 was administered orally. We examined the morphological changes in the intrahepatic biliary branches and quantitatively estimated density of mucus-producing glandular elements in the ductal wall by counting these glands per unit area. Dogs treated with 16,16-dimethyl prostaglandin E2 (group 1) demonstrated fibrous thickening of the ductal wall, moderate infiltration by inflammatory cells and severe adenomatous hyperplasia of the bile duct epithelium, including striking proliferation of the mucous glands. The mean number of these mucous glands per unit area (4 mm2) was 43.0 +/- 9.0 (mean +/- S.D.; range = 36 to 56). In contrast, in a control group whose members did not receive 16,16-dimethyl prostaglandin E2 (group 2), the mean number of mucous glands per unit area was 19.4 +/- 8.0 (range = 10 to 29), significantly lower than that in group 1, although histological examination revealed chronic inflammation in the region of the large bile duct similar to that in group 1. These findings suggest that the increase in the number of mucous glands that typically occur in the setting of bile stasis and biliary infection is enhanced by 16,16-dimethyl prostaglandin E2.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Bacteroides Infections; Bile Ducts, Intrahepatic; Cholestasis, Intrahepatic; Dogs; Escherichia coli Infections; Exocrine Glands; Female; Hyperplasia; Inflammation; Male; Mucus

The development of tolerance induced by subcutaneous or intraocular injections of lipopolysaccharide (LPS, Escherichia coli) in rat eyes has been studied. In addition, the ocular inflammatory responses to the reversed passive Arthus (RPA) reaction in the tolerant eyes were investigated. The tolerance in the eye after a single injection of LPS persisted for at least 42 days. Up to 42 days, vasodilatation, disruption of the blood-aqueous barrier, and leukocyte accumulation in the anterior chamber after a second injection of LPS were inhibited. Unilateral intraocular injection of LPS produced local tolerance, which was not observed in the contralateral eyes. The inflammatory reactions in response to RPA in the LPS-tolerant eyes were also significantly attenuated. It was also found that inflammatory reactions induced by RPA or 16,16-dimethyl prostaglandin E2 had no inhibitory effect on the responses to subsequent RPA or LPS administration, which indicated that initial inflammatory reactions do not render the tissues refractory to the response to a second stimuli. The results of this study suggest that some, as yet unknown, local changes in the ocular tissues caused by LPS may be involved in the development of tolerance.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Drug Tolerance; Escherichia coli; Eye Diseases; Immune Sera; Inflammation; Iris; Leukocytes; Lipopolysaccharides; Male; Ovalbumin; Proteins; Rats; Rats, Inbred Strains; Vasodilation