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-l (IL-1) production, by a human colonic epithelial cell line (HT29-Cl.16E). SNP was able to induce intracellular IL-lcr, production up to 10 h incubation, in a dose-dependent manner. Several experiments provide evidence that the NOS redox form, and not the free radical NO., is implicated in the IL-la production: (i) SIN-I, 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.