IL-1 is also known as lymphocyte-activating factor (LAF), endogenous pyrogen and catabolin. It displays a wide variety of biological activities and has been appraised clinically in several trials.

Two distinct forms of IL-1 exist: IL-1a and IL-1p. Although different gene products, and exhibiting only 20 per cent amino acid sequence homology, both of these molecules bind the same receptor and induce similar biological activities. The genes coding for IL-1a and -1p both reside on human chromosome number 2, and display similar molecular organization, both containing seven exons.

IL-1a and -1p are expressed as large (30 kDa) precursor molecules from which the mature polypeptide is released by proteolytic cleavage. Neither IL-1a and -1p possess any known secretory signal peptide, and the molecular mechanism by which they exit the cell remains to be characterized. Neither interleukin appears to be glycosylated.

IL-1a is initially synthesized as a 271 amino acid precursor, with the mature form containing 159 amino acids (17.5 kDa). This molecule appears to remain associated with the extracellular face of the cell membrane. IL-1p, initially synthesized as a 269 amino acid precursor, is released fully from the cell. The mature form released contains 153 amino acids and displays a molecular mass in the region of 17.3 kDa.

X-ray diffraction analysis reveals the three-dimensional structure of both IL-1 molecules to be quite similar. Both are globular proteins, composed of six strands of antiparallel p pleated sheet forming a 'barrel' that is closed at one end by a further series of p sheets.

A wide range of cells are capable of producing IL-1 (Table 9.4). Different cell types produce the different IL-1s in varying ratios. In fibroblasts and endothelial cells, both are produced in roughly similar ratios, whereas IL-1p is produced in larger quantities than IL-1a in monocytes. Activated macrophages appear to represent the major cellular source for IL-1.

The IL-1s induce their characteristic biological activities by binding to specific cell surface receptors present on sensitive cells. Two distinct receptors, type I and II, have been identified. Both IL-1a and IL-1p can bind both receptors. The type I receptor is an 80 kDa transmembrane glycoprotein. It is a member of the IgG superfamily. This receptor is expressed predominantly on fibroblasts, keratinocytes, hepatocytes and endothelial cells. The type II receptor is a 60 kDa transmembrane glycoprotein, expressed mainly on B-lymphocytes, bone marrow cells and polymorphonuclear leukocytes. It displays a very short (29 amino acid) intracellular domain,

Table 9.4 The range of cells capable of producing IL-1

T-lymphocytes B-lymphocytes

Vascular endothelial cells

Fibroblasts Astrocytes

Monocytes/macrophages NK cells

Large granular lymphocytes

Dendritic cells Microglia Glioma cells

Keratinocytes Chondrocytes and some studies suggest that IL-1s can induce a biological response only upon binding to the type I receptor.

The exact IL-1-mediated mechanism(s) of signal transduction remain to be clarified. A number of different signal transduction pathways have been implicated, including involvement of G-pro-teins. IL-1 has also been implicated in activation of protein kinase C by inducing the hydrolysis of phosphatidylethanolamine.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook

Post a comment