A redox-based mechanism for induction of interleukin-1 production by nitric oxide in a human colonic epithelial cell line (HT29-Cl.16E).
We evaluated the effects of two NO donors, sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1), characterized by alternative redox states, i.e. nitrosonium ion (NO+) and nitric oxide (NO.) respectively, on intracellular interleukin-1 (IL-1) production, by a human colonic epithelial cell line (HT29-Cl.16E). SNP was able to induce intracellular IL-1 alpha production up to 10 h incubation, in a dose-dependent manner. Several experiments provide evidence that the NO+ redox form, and not the free radical NO., is implicated in the IL-1 alpha production: (i) SIN-1, devoid of any NO+ character, led to a very weak IL-1 production as compared with SNP; (ii) the reductive action of a thiol such as cysteine on NO+ led to a dose-dependent increase in NO, concentration, measured as NO2-/NO3- accumulation, and to large decrease in IL-1 production. Dibutyryl cGMP had no effect on IL-1 production, this finding supporting the concept that a cGMP-independent pathway is involved in the intracellular signalling of NO+. Together these results point out that NO, depending on its redox form, is able to modulate IL-1 production in cultured colonic epithelial cells.
Groupe de Recherche Fonctions Sécrétoires des Epithélums Digestits, INSERM CJF 94-04, Faculté de Médecine, Nantes, France.
G
G
Vallette
A
A
Jarry
J E
JE
Branka
C L
CL
Laboisse
D002460:Cell Line; D004848:Epithelium / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism / Q000494:pharmacology; D019073:HT29 Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D007700:Kinetics; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009599:Nitroprusside / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D005609:Free Radicals; D007375:Interleukin-1; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine