| Description |
Cytokines comprise the molecular communication networks that allow cells to respond to their environments. Oncostatin M belongs to the interleukin-6 family of cytokines and has diverse effects on many different cell types. In various model systems, it has been shown to influence cell cycle progression, developmental regulation, and the inflammatory process. Therefore, it is difficult to classify oncostatin M as one type of effector molecule. The origins and regulation of oncostatin M expression have not been extensively examined. The goal of this dissertation was to identify and characterize oncostatin M expression in normal human tissues. Primary human monocytes secrete oncostatin M following activation with cytokines or bacterial components. Agonist treatment of monocytes results in activation of the Janus-kinase signal transducer and activator of transcription (JAK-STAT) pathway. Specifically, STAT5b was found to bind and activate the oncostatin M promoter at a STAT binding site located -180 base pairs before the transcriptional start site. In addition, oncostatin M was produced by epithelial cells as indicated by immunohistochemistry and in situ hybridization. In contrast to monocytes, primary epithelial cells appeared to synthesize oncostatin M constitutively. Oncostatin M expression was detected only in primary cells, not in transformed cell lines. This would suggest, with previous reports, that a lack of oncostatin M expression is associated with the transformed phenotype. In summary, the origins of oncostatin M in the normal human system were found to be activated monocytes, which synthesize oncostatin M following activation, and specific types of epithelial cells, which synthesize oncostatin M constitutively. |
