Recombinant human interleukin 1 alpha: purification and biological characterization.

Abstract

Interleukin 1 (IL 1) is a polypeptide hormone produced by activated macrophages that affects many different cell types involved in immune and inflammatory responses. The cloning and expression of a murine IL 1 cDNA in Escherichia coli encoding a polypeptide precursor of 270 amino acids has been reported, and expression of the carboxy-terminal 156 amino acids of this precursor in E. coli yields biologically active IL 1. By using the murine IL 1 cDNA as a probe, we have isolated its human homolog from cDNA generated to lipopolysaccharide-stimulated human leukocyte mRNA. Nucleotide sequence analysis of this cDNA predicts a protein of analysis of this cDNA predicts a protein of 271 amino acids (termed IL 1 alpha) which shows congruent to 61% homology to its murine counterpart but only 27% homology to a recently characterized human IL 1 precursor (IL 1 beta). We have expressed the carboxy-terminal 154 amino acids of IL 1 alpha in E. coli, purified this protein to homogeneity, and have compared it with pure recombinant murine IL 1 in several different IL 1 assays based on murine and human cells. Recombinant IL 1 is capable of stimulating T cell and fibroblast proliferation and inducing fibroblast collagenase and prostaglandin production, thus proving that a single molecule has many of the activities previously ascribed to only partially purified IL 1 preparations. Our results indicate that there exists a family of at least two human IL 1 genes (alpha and beta) whose dissimilar protein products have similar biological activities.

Therapeutic modulation of the liver immune microenvironment

“…[51] In contrast, the IL-1β precursor is released on necrotic cell death. [7,52] IL-1β is active in its precursor form and potently induces IL-1β. [53] These 2 prototypic inflammatory cytokines are rarely detected in the circulation even in case of substantial systemic inflammation and trigger substantial inflammatory symptoms when administered to humans at very low concentrations.…”

“…Many inflammatory events are accompanied by upregulation of pro-IL-1β mRNA/protein expression and activation and cleavage of pro-caspase-1 into active caspase-1, thereby cleaving pro-IL-1β into the active secreted form IL-1β 51 . In contrast, the IL-1β precursor is released on necrotic cell death 7,52 . IL-1β is active in its precursor form and potently induces IL-1β 53 .…”