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 red ox states, i.e. nitrosonium ion (NO+) and nitric oxide (NO.) respectiv ely, on intracellular interleukin-l (IL-1) production, by a human colo nic epithelial cell line (HT29-Cl.16E). SNP was able to induce intrace llular IL-lcr, production up to 10 h incubation, in a dose-dependent m anner. Several experiments provide evidence that the NOS redox form, a nd 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 producti on 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 pro duction. 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 produc tion in cultured colonic epithelial cells.