iNOS-dependent increase in colonic mucus thickness in DSS-colitic rats
(English)Manuscript (preprint) (Other academic)
Aim: To investigate colonic mucus thickness in vivo in health and during experimental inflammatory bowel disease.
Methods: Colitis was induced with 5% DSS for 9 days. The colon of anesthetized rats was mounted mucosal side up and studied with intravital microscopy. Using a micropipette, attached to a micromanipulator and a digimatic indicator, mucus thickness was measured. The unselective NOS inhibitor L-NNA, the selective iNOS inhibitor L-NIL and the unselective COX inhibitor diclofenac were used to assess the contributions of NOS and prostaglandins in the regulation of mucus thickness. C57Bl/6 and iNOS -/- mice were used to further investigate the role of iNOS in mucus regulation.
Results: Colitic rats had a thicker firmly adherent mucus layer than untreated control rats 9 days after the start of the experiment (88 ± 2 µm vs 76 ± 1 µm). During the course of the colitis-induction the thickness of the mucus layer first decreased, but from day 4 the mucus thickness was significantly thicker than in untreated rats. Diclofenac (5 mg/kg i.v.) reduced the mucus thickness comparably in colitic and untreated rats (-17 ± 6 µm vs -14 ± 2 µm). While L-NNA had no effect on mucus thickness in either DSS or untreated controls (+3 ± 2 µm vs +3 ± 1 µm), L-NIL reduced the mucus thickness significantly more in colitic rats than in untreated controls (-33 ± 4 µm vs -12 ± 1 µm). The importance of iNOS in maintaining mucus thickness was confirmed in iNOS -/- mice which had a thinner mucus thickness than control mice (35 ± 3 µm vs 50 ± 2 µm).
Conclusion: Colitic rats have a thicker firmly adherent colonic mucus layer and this effect is mediated by iNOS. Prostaglandins are involved in the regulation of base line mucus secretion.
Experimental colitis, DSS, mucus thickness, MUC2, iNOS, prostaglandins
Research subject Physiology
IdentifiersURN: urn:nbn:se:uu:diva-112500OAI: oai:DiVA.org:uu-112500DiVA: diva2:287680