Cytokines and their receptors: molecular mechanism of interleukin-6 gene repression by glucocorticoids.
Recent years have seen the discovery and molecular characterization of a bewildering array of cytokines and hematopoietic growth factors--and an even more complex description of their overlapping functions. The molecular cloning of a wide array of the cell-surface receptors for these cytokines has led to the recognition of classes of structurally related receptor superfamilies. The functional receptors for many of these cytokines (e.g., interleukin (IL)-2R and IL-6R) involve two distinct subunits; strikingly, the same beta subunit can interact with distinct alpha subunits to constitute the receptor for different cytokines (e.g., those for IL-3, IL-5, and granulocyte monocyte colony-stimulating factor). Considerable progress has also been made in defining the molecular mechanisms that underlie clinically relevant cytokine-related phenomena. As an example, the molecular mechanism by which glucocorticoids inhibit IL-6 gene expression has been shown to include the occlusion of the inducible enhancer and the basal promoter elements in the IL-6 promoter. Acute rejection episodes in renal transplant patients are accompanied by increases in serum IL-6 levels; the administration of glucocorticoids during these episodes leads to a rapid and marked decrease in IL-6 levels. It appears that the serum IL-6 level may be a useful diagnostic and prognostic indicator in the transplant patient.
Ray
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Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
Sehgal
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PB
D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes; D005938:Glucocorticoids / Q000502:physiology*; D006084:Graft Rejection / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D016030:Kidney Transplantation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D015213:Neuroimmunomodulation / Q000502:physiology; D009490:Neurosecretory Systems / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis
D016207:Cytokines; D005938:Glucocorticoids; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins