Bedeutung von Interleukin-6, Oncostatin M und Interleukin-31 für die biochemische und immunologische Barrierefunktion der Haut
type: CreativeWork
description: The barrier function of the human skin involves biochemical as well as immunological processes. The family of multidrug resistance-associated proteins (MRP) are efflux transporters which protect skin cells from xenobiotica and promote inflammatory defence responses against pathogens through the export of prostaglandins and leukotrienes. In the first part of this thesis we investigated the effect of interleukin-6 (IL-6) and oncostatin M (OSM) on the expression of MRP-1, -3, -4 and -5 in normal human epidermal keratinocytes and primary dermal fibroblasts. Using real-time PCR, RT-PCR, cDNA microarray, immunostaining and efflux assays we found that IL-6 in combination with its soluble receptor enhances MRP expression and activity in keratinocytes. Despite the expression of the OSM receptor (OSMR) we could not observe an increased expression of MRP-3 in keratinocytes while MRP-1 mRNA levels were elevated. On the other hand OSM turned out to be a more effective stimulator of MRP synthesis in dermal fibroblasts. Both cytokines induced a strong activation of STAT1 and STAT3 (signal transducer and activator of transcription) as well as the MAPK (mitogen-activated protein kinase) Erk1/2. In contrast to IL-6, OSM additionally activated protein kinase B/Akt and the stress-activated MAPK p38. While the activation of MAPK occurred transiently with a peak at 30 minutes, the tyrosine phosphorylation of STAT factors persisted over a time period of 24 hours. Using the MEK1 (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 in the OSM-mediated up-regulation of MRP-4 in dermal fibroblasts. It was known before that several inflammatory skin diseases show an enhanced expression of IL-6-type cytokines. This fact correlates well with the observed up-regulation of MRP-1 expression in lesional…
abstract: The barrier function of the human skin involves biochemical as well as immunological processes. The family of multidrug resistance-associated proteins (MRP) are efflux transporters which protect skin cells from xenobiotica and promote inflammatory defence responses against pathogens through the export of prostaglandins and leukotrienes. In the first part of this thesis we investigated the effect of interleukin-6 (IL-6) and oncostatin M (OSM) on the expression of MRP-1, -3, -4 and -5 in normal human epidermal keratinocytes and primary dermal fibroblasts. Using real-time PCR, RT-PCR, cDNA microarray, immunostaining and efflux assays we found that IL-6 in combination with its soluble receptor enhances MRP expression and activity in keratinocytes. Despite the expression of the OSM receptor (OSMR) we could not observe an increased expression of MRP-3 in keratinocytes while MRP-1 mRNA levels were elevated. On the other hand OSM turned out to be a more effective stimulator of MRP synthesis in dermal fibroblasts. Both cytokines induced a strong activation of STAT1 and STAT3 (signal transducer and activator of transcription) as well as the MAPK (mitogen-activated protein kinase) Erk1/2. In contrast to IL-6, OSM additionally activated protein kinase B/Akt and the stress-activated MAPK p38. While the activation of MAPK occurred transiently with a peak at 30 minutes, the tyrosine phosphorylation of STAT factors persisted over a time period of 24 hours. Using the MEK1 (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 in the OSM-mediated up-regulation of MRP-4 in dermal fibroblasts. It was known before that several inflammatory skin diseases show an enhanced expression of IL-6-type cytokines. This fact correlates well with the observed up-regulation of MRP-1 expression in lesional…
author: Dreuw, Alexandra
language: ger
keywords: info:eu-repo/classification/ddc/570, Biowissenschaften, Biologie, Signaltransduktion, Cytokine, Dermatitis, Haut, MRP-Proteine, Interleukin-31, Oncostatin M, skin, multidrug resistance-associated proteins, signal transduction, cytokines
date published: 2006
date modified: 2026-07-30T19:43:28Z
provider: RWTH Aachen University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Publikationsserver der RWTH Aachen University