Il-1 beta is an important immunoregulatory molecule which is released from human monocytes upon stimulation with LPS. Because this protein lacks a leader sequence, it is not """"""""packaged"""""""" within the endoplasmic recticulum and is therefore not released from the cells via the same mechanism as other commonly secreted proteins. The exact mechanism of release of IL-1 is not known, although one theory set forth suggests that IL-1 is released from monocytes following apoptotic cell death. The purpose of this study is to determine what effect M-CSF, a cytokine able to promote monocyte survival, has on the release of IL-1 beta from human monocytes. Using a variety of techniques, including radiolabeling of monocyte proteins and immunoprecipitation, we have thus far determined that pretreatment of monocytes with MCSF results in a decrease in the amount of IL-1 beta released from human monocytes. This decrease appears to be due specifically to a suppression in the release of IL-1 from the cells and not to changes in transcription, translation or enzymatic conversion of the IL-1 beta molecule. Recent studies have shown that a gene product, which appears to regulate apoptosis in some cells, is highly homologous to the IL-1 convertase enzyme (ICE). Therefore, we now plan to determine if the activation of ICE in human monocytes leads to apoptic cell death and if M-CSF treatment alters the induction of or activity of this enzyme.
