Regulation of ICE activity and ICE isoforms by LPS.

Abstract

Interleukin 1 beta (IL-1 beta) is a highly inducible proinflammatory cytokine. It is processed to its mature, secreted 17-kDa form by a cysteine endoprotease; the interleukin 1 beta converting enzyme (ICE). Regulation of IL-1 beta levels can be achieved both at transcriptional and translational level and in particular at the posttranslational, ICE catalysed, level. Thus, we examined ICE activity in rats under conditions of systemic stimulation by intraperitoneal (i.p.) injections of lipopolysaccharide (LPS) from E. coli, which are known to dramatically alter IL-1 beta mRNA and protein levels. ICE mRNA levels and endoprotease activity have also been found to be differentially regulated in the rat adrenal gland and rat brain after i.p. injections of LPS. An induction in ICE mRNA levels could be seen in the adrenal gland, the pituitary and in the hypothalamus after LPS treatment as measured by reverse transcription-polymerase chain reaction (RT-PCR), whereas the ICE endoprotease activity was increased in the pituitary and decreased in the hippocampus and in the adrenal gland. The discrepancy between increased mRNA level for ICE and decreased enzyme activity in the adrenals might be explained by the induction of ICE isoforms, some of which might be inhibitory for the enzyme activity and induced by LPS, yielding as a net effect a suppression of ICE activity.