Cyclosporin A, FK506 and dithranol after tyrosine-specific protein phosphorylation in HaCaT keratinocytes
| Autor: | Gregor Nussbaum, Manfred Goos, P.M. Burger, Hans M. Ockenfels, T Schultewolter |
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| Rok vydání: | 1995 |
| Předmět: |
Intracellular Fluid
Keratinocytes Indoles Dermatology Biology Tacrolimus Cell Line Organ Culture Techniques Cyclosporin a Dithranol medicine Humans Psoriasis Tyrosine Phosphorylation Phosphotyrosine Protein kinase C Protein Kinase C Skin Proteins General Medicine Anthralin Protein-Tyrosine Kinases Immunohistochemistry Cell biology HaCaT medicine.anatomical_structure Biochemistry Cyclosporine Signal transduction Keratinocyte medicine.drug Signal Transduction |
| Zdroj: | Archives of dermatological research. 287(3-4) |
| ISSN: | 0340-3696 |
| Popis: | Protein tyrosine kinases (PTKs) are closely related to cell growth, proliferation and differentiation. In keratinocytes, various growth factor receptors and cytosolic proteins, including the EGF and IGF receptors, the proteins of the src family and others, exhibit PTK activity. In psoriatic epidermis an increased level of EGF receptors and their ligand TGF-alpha has been found, and this is thought to be one reason for the pathological hyperproliferation of keratinocytes in this disease. Oral treatment with cyclosporin A (CsA) and FK506 or topical treatment with dithranol lead to an improvement in psoriasis. In the present study we examined the effect of these three drugs on the cellular content of phosphorylated tyrosines in highly proliferative HaCaT keratinocytes. HaCaT keratinocytes can be used as a model for highly proliferative epidermis, e.g. psoriatic epidermis. CsA had no effect whereas FK506 and dithranol reduced the phosphorylation of tyrosine residues in HaCaT keratinocytes. The activation of serine/threonine protein kinase C (PKC) is known to downregulate PTKs. Therefore we incubated keratinocytes with the selective PKC inhibitor Ro 31-8220 in addition to the other drugs. Only after the addition of Ro 31-8220 to FK506-treated keratinocytes was the phosphotyrosine (p-tyr) level elevated, but this was only one-third of the increase measured without additional therapeutic drugs. We assume that an induction of PKC alone is not responsible for the reduced p-tyr level after treatment with dithranol and FK506. FK506 and CsA affect the p-tyr signal transduction pathways of HaCaT keratinocytes in different ways, indicating distinct mechanisms of action of these drugs on keratinocytes. |
| Databáze: | OpenAIRE |
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