IL-27 Regulates IL-18 binding protein in skin resident cells.
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3384590?pdf=render |
| _version_ | 1811264686346207232 |
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| author | Miriam Wittmann Rosella Doble Malte Bachmann Josef Pfeilschifter Thomas Werfel Heiko Mühl |
| author_facet | Miriam Wittmann Rosella Doble Malte Bachmann Josef Pfeilschifter Thomas Werfel Heiko Mühl |
| author_sort | Miriam Wittmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T20:07:40Z |
| format | Article |
| id | doaj.art-26852842a75d44c0a57ab34c4222d3b3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T20:07:40Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-26852842a75d44c0a57ab34c4222d3b32022-12-22T03:18:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3875110.1371/journal.pone.0038751IL-27 Regulates IL-18 binding protein in skin resident cells.Miriam WittmannRosella DobleMalte BachmannJosef PfeilschifterThomas WerfelHeiko MühlIL-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.http://europepmc.org/articles/PMC3384590?pdf=render |
| spellingShingle | Miriam Wittmann Rosella Doble Malte Bachmann Josef Pfeilschifter Thomas Werfel Heiko Mühl IL-27 Regulates IL-18 binding protein in skin resident cells. PLoS ONE |
| title | IL-27 Regulates IL-18 binding protein in skin resident cells. |
| title_full | IL-27 Regulates IL-18 binding protein in skin resident cells. |
| title_fullStr | IL-27 Regulates IL-18 binding protein in skin resident cells. |
| title_full_unstemmed | IL-27 Regulates IL-18 binding protein in skin resident cells. |
| title_short | IL-27 Regulates IL-18 binding protein in skin resident cells. |
| title_sort | il 27 regulates il 18 binding protein in skin resident cells |
| url | http://europepmc.org/articles/PMC3384590?pdf=render |
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