Abstract
Analysis of the cDNA encoding murine interleukin (IL) 17 (cytotoxic T lymphocyte associated antigen 8) predicted a secreted protein sharing 57% amino acid identity with the protein predicted from ORF13, an open reading frame of Herpesvirus saimiri. Here we report on the cloning of human IL-17 (hIL-17), the human counterpart of murine IL-17. hIL-17 is a glycoprotein of 155 amino acids secreted as an homodimer by activated memory CD4+ T cells. Although devoid of direct effects on cells of hematopoietic origin, hIL-17 and the product of its viral counterpart, ORF13, stimulate epithelial, endothelial, and fibroblastic cells to secrete cytokines such as IL-6, IL-8, and granulocyte-colony-stimulating factor, as well as prostaglandin E2. Furthermore, when cultured in the presence of hIL-17, fibroblasts could sustain the proliferation of CD34+ hematopoietic progenitors and their preferential maturation into neutrophils. These observations suggest that hIL-17 may constitute (a) an early initiator of the T cell-dependent inflammmatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.
MeSH terms
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Amino Acid Sequence
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Animals
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Arthritis, Rheumatoid / immunology
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Base Sequence
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Cytokines / biosynthesis*
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Dinoprostone / biosynthesis
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / immunology*
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Fibroblasts / immunology
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Granulocyte Colony-Stimulating Factor / biosynthesis
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Hematopoiesis
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / immunology*
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Herpesvirus 2, Saimiriine / genetics
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Herpesvirus 2, Saimiriine / metabolism
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Humans
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Inflammation
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Interferon-gamma / pharmacology
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Interleukin-17
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Interleukin-6 / biosynthesis
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Interleukin-8 / biosynthesis
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Interleukins / biosynthesis*
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Interleukins / chemistry
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Interleukins / immunology
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Lymphocytes / immunology
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Macromolecular Substances
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Mice
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Molecular Sequence Data
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Open Reading Frames
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Recombinant Proteins / biosynthesis
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Reference Values
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Sequence Homology, Amino Acid
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Skin / immunology
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Stromal Cells / drug effects
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Stromal Cells / immunology
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Synovial Membrane / immunology
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T-Lymphocytes / immunology*
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Transfection
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Tumor Necrosis Factor-alpha / pharmacology
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Viral Proteins / biosynthesis
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Viral Proteins / chemistry
Substances
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Cytokines
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Interleukin-17
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Interleukin-6
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Interleukin-8
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Interleukins
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Macromolecular Substances
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ORF13 protein, Herpesvirus saimiri
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Viral Proteins
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Granulocyte Colony-Stimulating Factor
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Interferon-gamma
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Dinoprostone