Molecular Cloning and Expression of Rat Interleukin-1α cDNA

Abstract

A cDNA sequence coding for rat interleukin-1α (IL-1α) has been isolated from a cDNA library that was prepared with mRNA derived from LPS-stimulated rat peritoneal macrophages by using human IL-1α cDNA as a probe. The rat cDNA encodes a 270 amino acid residue protein which is homologous (65%) to human IL-la. The rat cDNA sequence under SV40 early promoter directed the synthesis of biologically active IL-1 in monkey COS-1 cells. Rat IL-1α mRNA is not expressed in spleen, lung, liver or brain, and is also not expressed in these organs of LPS-treated rat except spleen. This suggests that IL-1α is not produced constitutively in various tissues and LPS is not sufficient to induce IL-1α in most tissues. Our data indicate that the IL-1 activities which have been reported to be produced in the brain are not of α type. We have constructed a plasmid expressing the carboxy terminal 156 amino acids in Escherichia coli. Recombinant rat IL-1α produced in COS cells or E. coli has cytotoxic activity against the human melanoma cell line A375S1 (GIF activity), which has been reported to be sensitive to human IL-1α and IL-1β. This suggests that GIF activity is common to IL-ls derived from various sources.