Interleukin-6-Type Cytokines Upregulate Expression of Multidrug Resistance-Associated Proteins in NHEK and Dermal Fibroblasts
| Autor: | Jens M. Baron, Alexandra Dreuw, Felipe Rodríguez, Frank K. Jugert, Yvonne Marquardt, Sylvia Joussen, Ruth Heise, Heike M. Hermanns, Hans F. Merk, Peter C. Heinrich |
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| Rok vydání: | 2005 |
| Předmět: |
Keratinocytes
MAPK/ERK pathway ATP Binding Cassette Transporter Subfamily B MAP Kinase Signaling System medicine.medical_treatment Gene Expression Cell Communication Oncostatin M Dermatology Protein Serine-Threonine Kinases Biochemistry Proinflammatory cytokine Downregulation and upregulation Proto-Oncogene Proteins medicine Humans Psoriasis RNA Messenger STAT3 Molecular Biology Cells Cultured integumentary system biology Interleukin-6 Kinase Lichen Planus Dermis Cell Biology Fibroblasts Immunohistochemistry Molecular biology Growth Inhibitors Up-Regulation Cytokine Immunology biology.protein STAT protein Mitogen-Activated Protein Kinases Peptides Proto-Oncogene Proteins c-akt |
| Zdroj: | Journal of Investigative Dermatology. 124:28-37 |
| ISSN: | 0022-202X |
| DOI: | 10.1111/j.0022-202x.2004.23499.x |
| Popis: | Normal human epidermal keratinocytes (NHEK) and dermal fibroblasts express a cell-specific pattern of efflux transport proteins. Since regulatory mechanisms for these transporters in cells of the human skin were unknown, we analyzed the influence of inflammatory cytokines on the expression of multidrug resistance-associated proteins (MRP1, 3, 4, 5). Using real-time PCR, RT-PCR, cDNA microarray, immunostaining and efflux assays we demonstrated that stimulation of NHEK and primary human dermal fibroblasts with interleukin-6 (IL-6), in combination with its soluble alpha-receptor, or oncostatin M (OSM) for 24-72 h resulted in an upregulation of MRP expression and activity. Both cytokines induced a strong activation of signal transducer and activator of transcription (STAT)1 and STAT3 as well as the mitogen-activated protein kinase (MAPK) Erk1/2. OSM additionally activated proteinkinase B strongly. Using the MAPK/extracellular signal-regulated kinase kinase 1-specific inhibitor U0126 we could exclude a stimulatory effect of MAPK on MRP gene expression. Inhibition of the phosphatidylinositol 3-kinase, however, indicated that this pathway might be involved of OSM-mediated upregulation of MRP4 in dermal fibroblasts. Several inflammatory skin diseases show an enhanced expression of IL-6-type cytokines. Correspondingly, upregulation of MRP expression was found in lesional skin taken from patients with psoriasis and lichen planus. |
| Databáze: | OpenAIRE |
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