TY  - JOUR
A1  - Wittmann, Miriam
A1  - Doble, Rosella
A1  - Bachmann, Malte
A1  - Pfeilschifter, Josef
A1  - Werfel, Thomas
A1  - Mühl, Heiko
T1  - IL-27 regulates IL-18 binding protein in skin resident cells
T2  - PLoS One
N2  - IL-18 is an important mediator involved in chronic inflammatory conditions such as cutaneous lupus erythematosus, psoriasis and chronic eczema. An imbalance between IL-18 and its endogenous antagonist IL-18 binding protein (BP) may account for increased IL-18 activity. IL-27 is a cytokine with dual function displaying pro- and anti-inflammatory properties. Here we provide evidence for a yet not described anti-inflammatory mode of action on skin resident cells. Human keratinocytes and surprisingly also fibroblasts (which do not produce any IL-18) show a robust, dose-dependent and highly inducible mRNA expression and secretion of IL-18BP upon IL-27 stimulation. Other IL-12 family members failed to induce IL-18BP. The production of IL-18BP peaked between 48–72 h after stimulation and was sustained for up to 96 h. Investigation of the signalling pathway showed that IL-27 activates STAT1 in human keratinocytes and that a proximal GAS site at the IL-18BP promoter is of importance for the functional activity of IL-27. The data are in support of a significant anti-inflammatory effect of IL-27 on skin resident cells. An important novel property of IL-27 in skin pathobiology may be to counter-regulate IL-18 activities by acting on keratinocytes and importantly also on dermal fibroblasts.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25551
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-255519
SN  - 1932-6203
VL  - 7
IS  - (6):e38751
PB  - PLoS
CY  - Lawrence, Kan.
ER  -