The mouse interleukin 1 receptor antagonist protein: gene structure and regulation in vitro

The interleukin 1 receptor antagonist (IL-1ra) protein is an inhibitor of the pro-inflammatory cytokine interleukin 1. We have sequenced the mouse gene encoding the monocyte form of IL-1ra (IL-1rn) and compared it with the sequence of the human homologue. In addition to high levels of similarity between the coding regions of the two genes, portions of the introns show surprisingly high levels of identity. In order to develop an in vitro model system to investigate the regulation of IL-1ra induction, three differently responding mouse macrophage cell lines were stimulated with lipopolysaccharide. The kinetics and magnitude of IL-1ra mRNA accumulation was cell-line specific indicating that IL-1ra synthesis in response to inducing agents varies according to the phenotype of the cell. Analysis of the relative transcription rate and the half life of the mouse IL-1ra mRNA indicate that IL-1ra mRNA accumulation in macrophages following LPS treatment is due primarily to an increase in transcription rate rather than to increased stability.