REGULATION OF ICE ACTIVITY AND ICE ISOFORMS BY LPS

Interleukin 1 beta (IL-1 beta) is a highly inducible proinflammatory c ytokine. It is processed to its mature, secreted 17-kDa form by a cyst eine endoprotease; the interleukin 1 beta converting enzyme (ICE), Reg ulation of IL-1 beta levels can be achieved both at transcriptional an d translational level and in particular at the posttranslational, ICE catalysed, level. Thus, we examined ICE activity in rats under conditi ons of systemic stimulation by intraperitoneal (i.p.) injections of li popolysaccharide (LPS) from E. coli, which are known to dramatically a lter IL-1 beta mRNA and protein levels. ICE mRNA levels and endoprotea se activity have also been found to be differentially regulated in the rat adrenal gland and rat brain after i.p. injections of LPS. An indu ction in ICE mRNA levels could be seen in the adrenal gland, the pitui tary and in the hypothalamus after LPS treatment as measured by revers e transcription-polymerase chain reaction (RT-PCR), whereas the ICE en doprotease activity was increased in the pituitary and decreased in th e hippocampus and in the adrenal gland. The discrepancy between increa sed mRNA level for ICE and decreased enzyme activity in the adrenals m ight be explained by the induction of ICE isoforms, some of which migh t be inhibitory for the enzyme activity and induced by LPS, yielding a s a net effect a suppression of ICE activity.