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 a couple of theories have been set forth. The purpose of this study is to determine the mechanism of release of IL-1 beta from human monocytes and thereby gain an understanding of the factors controlling its release. 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. Furthermore, through crosslinking studies, we have found that the pro form of IL-1 beta appears to be associated with another protein within these cells. Studies are currently underway aimed at identifying this protein and determining whether it plays a significant role in the release of IL-1 beta. If so, we plan to determine if the levels of this protein are altered by MCSF treatment.
