Interleukin-1 beta and lipopolysaccharide decrease soluble guanylyl cyclase in brain cells: NO-independent destabilization of protein and NO-dependent decrease of mRNA.

We previously showed that soluble guanylyl cyclase (sGC) is down-regulated in astroglial cells after exposure to LPS. Here, we show that this effect is not mediated by released IL-1beta but that this cytokine is also able to decrease NO-dependent cGMP accumulation in a time- and concentration-dependent manner. The effect of IL-1beta is receptor-mediated, mimicked by tumor necrosis factor-alpha and involves a decrease in sGC activity and protein. IL-1beta and LPS decrease the half-life of the sGC beta1 subunit by a NO-independent but transcription- and translation-dependent mechanism. Additionally, both agents induce a NO-dependent decrease of sGC subunit mRNA. Decreased sGC subunit protein and mRNA levels are also observed in adult rat brain after focal injection of IL-1beta or LPS.