TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL REGULATION OF INTERLEUKIN-1 GENE-EXPRESSION - REVIEW

Interleukin 1-alpha (IL-1-alpha) and beta (IL-1-beta) are proinflammatory cytokines that are encoded by distinct genes, but share most biological activities. During the past several years, intense investigation has focused on elucidating the molecular basis for the regulation of IL-1-alpha and beta-gene expression. While the overall organization of both genes is conserved in mammals, the DNA sequence homology is surprisingly limited. This supports the growing body of evidence suggesting that each gene is regulated by distinct cis- and trans-acting elements. Most recently, novel regulatory DNA sequence elements and several nuclear regulatory proteins have been identified, which ultimately participate in the control of IL-1-beta-gene transcription. In addition to transcriptional controls, the stability of IL-1 mRNA can be selectively regulated by various inducing stimuli and other cytokines. Taken together, these transcriptional and post-transcriptional regulatory mechanisms provide stringent, yet flexible, control over expression of the IL-1-alpha and beta-genes.