IL-1 alpha and IL-1 beta are structurally related polypeptides that
show approximately 25% homology at the amino acid level. Both are synthesized
as 31 kDa precursors that are subsequently cleaved into mature proteins of
approximately 17.5 kDa. Cleavage of the IL-1 beta precursor by Caspase-1/ICE is a
key step in the inflammatory response. Neither IL-1 alpha nor IL-1 beta contains a
typical hydrophobic signal peptide, but evidence suggests that these factors
can be secreted by non-classical pathways. A portion of unprocessed IL-1 alpha can
be presented on the cell membrane and may retain biological activity. The
precursor form of IL-1 beta, unlike the IL-1 alpha precursor, shows little or no
biological activity in comparison to the processed form. Both unprocessed and
mature forms of IL-1 beta are exported from the cell.
IL-1 alpha and IL-1 beta exert their effects through
immunoglobulin superfamily receptors that additionally bind IL-1ra. The 80 kDa
transmembrane type I receptor (IL-1 RI) is expressed on T cells, fibroblasts,
keratinocytes, endothelial cells, synovial lining cells, chondrocytes, and
hepatocytes. The 68 kDa transmembrane type II receptor (IL-1 RII) is expressed
on B cells, neutrophils, and bone marrow cells. The two IL-1 receptor types
show approximately 28% homology in their extracellular domains but differ
significantly in that the type II receptor has a cytoplasmic domain of only 29
amino acids (aa), whereas the type I receptor has a 213 aa cytoplasmic domain.
IL-1 RII does not appear to signal in response to IL-1 and may function as a
decoy receptor that attenuates IL-1 function. The IL-1 receptor accessory
protein (IL-1 RAcP) associates with IL-1 RI and is required for IL-1 RI signal
transduction. IL-1ra is a secreted molecule that functions as a competitive
inhibitor of IL-1. Soluble forms of both IL-1 RI and IL-1 RII have been
detected in human plasma, synovial fluids, and the conditioned media of several
human cell lines. In addition, IL-1 binding proteins that resemble soluble IL-1
RII are encoded by vaccinia and cowpox viruses.
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