Interleukin 1 beta (IL-1 beta) and the IL-1 beta-alpha 2-macroglobulin complex upregulate the platelet-derived growth factor alpha-receptor on rat pulmonary fibroblasts
| Autor: | James C. Bonner, Pamela M. Lindroos, P G Coin, Alvaro Osornio-Vargas |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Receptor Platelet-Derived Growth Factor alpha Platelet-derived growth factor medicine.medical_treatment Clinical Biochemistry Becaplermin Alpha (ethology) Methylamines chemistry.chemical_compound Thioredoxins Internal medicine medicine Animals Humans Receptors Platelet-Derived Growth Factor alpha-Macroglobulins RNA Messenger Fibroblast Beta (finance) Receptor Lung Molecular Biology Interleukin 12 receptor beta 1 subunit Cells Cultured Platelet-Derived Growth Factor biology Chemotaxis Growth factor DNA Proto-Oncogene Proteins c-sis Cell Biology Fibroblasts Rats Up-Regulation medicine.anatomical_structure Endocrinology chemistry biology.protein Cattle Mitogens Cell Division Platelet-derived growth factor receptor Interleukin-1 |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 13:455-465 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/ajrcmb.13.4.7546776 |
| Popis: | Fibroblasts are the primary proliferating cell type in pulmonary fibrosis. We previously showed that inorganic, fibrogenic particles alter the platelet-derived growth factor (PDGF) receptor system on rat lung fibroblasts (Bonner, J. C., et al. 1993, J. Clin. Invest 92:425-430). In lung fibroblasts, PDGF is the most potent proliferative cytokine, and the responses to PDGF isoforms depend on the relative amounts of two PDGF receptors (PDGF-R alpha and PDGF-R beta). Interleukin 1 beta (IL-1 beta) production by lung macrophages is increased following exposure to fibrogenic particles. We have examined the role of IL-1 beta in regulating the lung fibroblast PDGF receptor system. IL-1 beta induced a 10-fold increase in the number of binding sites for [125I]PDGF-AA, caused a 2-fold increase in affinity of [125I]PDGF-AB, but it had no effect on [125I]PDGF-BB binding. PDGF-R alpha gene expression was increased 5-fold after 4 h of IL-1 beta treatment. IL-1 beta increased the proliferative and chemotactic response to PDGF isoforms in the following order of potency: AA > AB > BB. IL-1 beta was tested for its ability to cause increased [125I]PDGF-AA binding when complexed to its binding protein, alpha 2-macroglobulin (alpha 2M). IL-1 beta bound covalently to fast methyl-amine-activated alpha 2M (alpha 2M-MA). IL-1 beta-alpha 2M-MA or alpha 2M-MA alone possessed minimal activity for inducing an increase in [125I]PDGF-AA binding. However, treatment of the IL-1 beta-alpha 2M complex with thioredoxin, which released bioactive IL-1 beta that was covalently bound to alpha 2M, maximally increased [125I]PDGF-AA binding to the same extent as free IL-1 beta. These results indicate that the fibroblast response to PDGF isoforms is modulated by a complex interaction involving IL-1 beta, alpha 2M, and thioredoxin, all of which are produced in vivo by activated macrophages. |
| Databáze: | OpenAIRE |
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