Fibroblasts Isolated from Normal Lungs and Those with Idiopathic Pulmonary Fibrosis Differ in Interleukin-6/gp130-Mediated Cell Signaling and Proliferation
| Autor: | Amelia K. Scaffidi, Steven E. Mutsaers, GJ Laurent, Neil L. A. Misso, Robin J. McAnulty, Darryl A. Knight, Yuben Moodley, Carmel B. Keerthisingam, Philip J. Thompson |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_treatment Pulmonary Fibrosis Hyperphosphorylation Cell Cycle Proteins Biology Pathology and Forensic Medicine Idiopathic pulmonary fibrosis Antigens CD Pulmonary fibrosis medicine Cytokine Receptor gp130 Humans Cyclin-Dependent Kinase Inhibitor p19 Enzyme Inhibitors Interleukin 6 Lung Cells Cultured Cyclin-Dependent Kinase Inhibitor p16 Membrane Glycoproteins Interleukin-6 Tumor Suppressor Proteins Interleukin respiratory system Fibroblasts Oligonucleotides Antisense medicine.disease Glycoprotein 130 Interleukin-11 Actins Cyclin-Dependent Kinases respiratory tract diseases Interleukin 11 DNA-Binding Proteins Enzyme Activation Cytokine Immunology Cancer research biology.protein Trans-Activators Mitogen-Activated Protein Kinases Mitogens Cell Division Cyclin-Dependent Kinase Inhibitor p27 Regular Articles Signal Transduction |
| Popis: | Interleukin (IL)-6 and IL-11 are elevated in a variety of lung conditions and may impact on repair mechanisms in chronic inflammatory disorders. However, the mechanisms by which these cytokines influence fibroblast proliferation in normal and disease states have not been previously addressed. We examined the effect of these cytokines on proliferation and cell-cycle kinetics of primary human lung fibroblasts obtained from normal patients and patients with idiopathic pulmonary fibrosis (IPF). IL-6 inhibited the proliferation of normal fibroblasts due to the sustained phosphorylation of STAT-3 and production of the cyclin-dependent kinase inhibitor p19(INK4D). In contrast IL-6 was mitogenic for IPF fibroblasts due to the sustained activation of MAPK, which in turn inhibited the production of p27(Kip1), allowing activation of cyclin D(1) and hyperphosphorylation of retinoblastoma protein. IL-11 was mitogenic for both normal and IPF fibroblasts. These results provide strong evidence for a fundamental abnormality in a cytokine-signaling pathway, as opposed to alterations in cytokine production, in the pathogenesis of IPF. |
| Databáze: | OpenAIRE |
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