Colitis and interleukin 1beta up-regulate inducible nitric oxide synthase and superoxide dismutase in rat myenteric neurons.
OBJECTIVE
Manganese superoxide dismutase (MnSOD) is rapidly induced in myenteric plexus neurons (MPNs) in acute colitis and may protect cells from nitric oxide toxicity. Inducible nitric oxide synthase (iNOS) regulation was examined in acute colitis, and MnSOD and iNOS were examined in primary cultures of MPNs.


METHODS
Acute colitis in rats was induced with 5% acetic acid. iNOS messenger RNA (mRNA) was analyzed by Northern analysis, and reduced nicotinamide adenine dinucleotide phosphate diaphorase was used to identify potential NO synthase activity. MnSOD and iNOS mRNA levels were evaluated in cultured MPNs after treatment with tumor necrosis factor alpha, interleukin (IL) 1beta, or IL-6. iNOS and MnSOD protein expression in control and IL-1beta-treated neurons was evaluated by immunofluorescence microscopy.


RESULTS
iNOS mRNA was detected in the mucosal and muscularis layers after the initiation of colitis. Reduced nicotinamide adenine dinucleotide phosphate diaphorase localized NO synthase activity to MPNs in controls and in epithelial cells and MPNs in the inflamed colon. In MPN cultures, tumor necrosis factor alpha and IL-1beta treatment resulted in induction of MnSOD, but only IL-1beta induced iNOS. Immunolocalization confirmed that the neurons were the primary source of iNOS and MnSOD.


CONCLUSIONS
Induction of MnSOD and iNOS are coordinated and may limit NO cytotoxicity. The function of iNOS in gut neurons remains to be delineated.
Valentine
J F
JF
Division of Gastroenterology, Department of Medicine, University of Florida, Gainesville, USA.
Tannahill
C L
CL
Stevenot
S A
SA
Sallustio
J E
JE
Nick
H S
HS
Eaker
E Y
EY
D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000201:enzymology*; D004790:Enzyme Induction; D019084:Fluorescent Antibody Technique, Indirect; D007375:Interleukin-1 / Q000494:pharmacology*; D009197:Myenteric Plexus / Q000201:enzymology*; D009474:Neurons / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase