title: iNOS-dependent increase in colonic mucus thickness in DSS-colitic rats.
abstract: OBJECTIVE
  To investigate colonic mucus thickness in vivo in health and during experimental inflammatory bowel disease.
  
  
  METHODS
  Colitis was induced with 5% DSS in drinking water for 8 days prior to experiment, when the descending colonic mucosa of anesthetized rats was studied using intravital microscopy. Mucus thickness was measured with micropipettes attached to a micromanipulator. To assess the contributions of NOS and prostaglandins in the regulation of colonic mucus thickness, the non-selective NOS-inhibitor L-NNA (10 mg/kg bolus followed by 3 mg/kg/h), the selective iNOS-inhibitor L-NIL (10 mg/kg bolus followed by 3 mg/kg/h) and the non-selective COX-inhibitor diclofenac (5 mg/kg) were administered intravenously prior to experiment. To further investigate the role of iNOS in the regulation of colonic mucus thickness, iNOS -/- mice were used.
  
  
  RESULTS
  Colitic rats had a thicker firmly adherent mucus layer following 8 days of DSS treatment than untreated rats (88±2 µm vs 76±1 µm). During induction of colitis, the thickness of the colonic mucus layer initially decreased but was from day 3 significantly thicker than in untreated rats. Diclofenac reduced the mucus thickness similarly in colitic and untreated rats (-16±5 µm vs -14±2 µm). While L-NNA had no effect on colonic mucus thickness in DSS or untreated controls (+3±2 µm vs +3±1 µm), L-NIL reduced the mucus thickness significantly more in colitic rats than in controls (-33±4 µm vs -10±3 µm). The importance of iNOS in regulating the colonic mucus thickness was confirmed in iNOS-/- mice, which had thinner colonic mucus than wild-type mice (35±3 µm vs 50±2 µm, respectively). Furthermore, immunohistochemistry revealed increased levels of iNOS in the colonic surface epithelium following DSS treatment.
  
  
  CONCLUSIONS
  Both prostaglandins and nitric oxide regulate basal colonic mucus thickness. During onset of colitis, the thickness of the mucus layer is initially reduced followed by an iNOS mediated increase.
authors: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors: Olof
authors: O
authors: Schreiber
authors: Joel
authors: J
authors: Petersson
authors: Tomas
authors: T
authors: Waldén
authors: David
authors: D
authors: Ahl
authors: Stellan
authors: S
authors: Sandler
authors: Mia
authors: M
authors: Phillipson
authors: Lena
authors: L
authors: Holm
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000201:enzymology*; D003106:Colon / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D020397:Goblet Cells / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C090663:N(6)-(1-iminoethyl)lysine; D011453:Prostaglandins; D019335:Nitroarginine; D009569:Nitric Oxide; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008239:Lysine
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