Regulation of cytokine gene expression.

Following the isolation and characterization of many cytokine genes, we began to understand the mechanisms regulating cytokine gene expression. Needless to say, understanding the mechanisms by which induction of gene expression occurs in a transient, cell type-specific manner in response to extracellular inducers is a central issue in eukaryotic molecular biology. The cytokine systems represent suitable models for studying the mechanisms regulating gene expression, since the expression of cytokines appears to be tightly regulated by restricted types of cells and inducers. At present, cis-acting DNA sequences involved in gene regulation have been identified in only a few cytokine genes. Little is known about the nature of factors regulating the cytokine gene expression. Of particular interest are the mechanisms by which the extracellular stimulation of the cells delivers signals in the nucleus and how they turn on the otherwise nonoperative transcription machinery. In many cases, the induction of the genes will involve the activation of preexisting factors rather than the de novo protein synthesis by modifications of the factors. Dysregulation of cytokine gene expression may be caused by chromosomal alterations or by infection of viruses that induce activation or inactivation of the expression machinery. This process may be crucial in the etiology of various diseases including neoplasms. To understand the complex nature of cytokine action in the regulation of cell proliferation, differentiation, and function, more attention should also be focused on the genes encoding the respective receptors.