CYCLOSPORINE, FK506, MYCOPHENOLATE MOFETIL, AND PREDNISOLONE DIFFERENTIALLY MODULATE CYTOKINE GENE EXPRESSION IN HUMAN AIRWAY-DERIVED EPITHELIAL CELLS
| Autor: | Jab Timmerman, Peter Borger, Gh Koeter, Hf Kauffman, J Scholma, Jwk van den Berg |
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| Rok vydání: | 2000 |
| Předmět: |
MECHANISM
PHARMACOKINETICS Transcription Genetic Prednisolone medicine.medical_treatment Respiratory System NF-KAPPA-B Gene Expression Pharmacology Biology Mycophenolate Tacrolimus Mycophenolic acid CALCINEURIN Proinflammatory cytokine ACTIVATION medicine Humans GLUCOCORTICOIDS Interleukin 8 Lung Cells Cultured LUNG TRANSPLANTATION Transplantation IMMUNOSUPPRESSION Dose-Response Relationship Drug IL-8 Interleukin-6 Interleukin-8 Interleukin Epithelial Cells Mycophenolic Acid Cytokine Immunology Cyclosporine Respiratory Physiological Phenomena Cytokines Respiratory epithelium MESSENGER-RNA Immunosuppressive Agents medicine.drug |
| Zdroj: | Transplantation, 69(7), 1408-1413. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/00007890-200004150-00034 |
| Popis: | Background. The immunosuppressive effects of cyclosporine (CsA), tacrolimus (FK506), mycophenolate mofetil (MMF), and prednisolone in cells from the immunological compartment are well documented. In contrast, limited information is available with respect to the effects of these immunosuppressive drugs on airway-epithelial cells, although these cells may contribute to the development of obliterative bronchiolitis (OB) through the production of interleukin (IL)-6 and IL-8. Methods. We studied the production of IL-6 and IL-8 proteins by airway-derived epithelial cell lines and primary epithelial cell cultures obtained from lung brushings. Transcriptional mechanisms were detected by transient transfections. Results. We demonstrate that CsA dose dependently induces the production of the proinflammatory cytokines IL-6 and IL-8 in both cell lines and primary epithelial cells. FK506 and MMF were also able to upregulate IL-8, although the effect was less dramatic than observed for CsA. Low concentrations of prednisolone (0.01 and 0.001 mu g/ml) enhanced IL-6 and IL-8 secretion, whereas concentrations greater than or equal to 0.01 mu g/ml significantly diminished IL-6 secretion. Furthermore, we showed that CsA and prednisolone mediate their effects at the transcriptional level. Conclusions. The data provide evidence that relevant concentrations of CsA and MMF in vivo may enhance the inflammatory processes in the lower airways of patients after lung transplantation. |
| Databáze: | OpenAIRE |
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