Cargando…
Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model
The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result i...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108310/ https://www.ncbi.nlm.nih.gov/pubmed/27537526 http://dx.doi.org/10.1038/cddis.2016.201 |
_version_ | 1782467333675024384 |
---|---|
author | Palombo, R Savini, I Avigliano, L Madonna, S Cavani, A Albanesi, C Mauriello, A Melino, G Terrinoni, A |
author_facet | Palombo, R Savini, I Avigliano, L Madonna, S Cavani, A Albanesi, C Mauriello, A Melino, G Terrinoni, A |
author_sort | Palombo, R |
collection | PubMed |
description | The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result in pathological changes. Some common skin diseases, such as psoriasis, are characterized by hyperproliferation accompanied by inflammatory reactions, suggesting that molecules with topical anti-inflammatory and ROS scavenging abilities may be useful for their treatment. Here we investigate the potential of the flavone Luteolin-7-glucoside (LUT-7G) as a treatment for psoriasis. We show that LUT-7G leads to a modification of the cell cycle and the induction of keratinocyte differentiation, with modification of energy, fatty acid, and redox metabolism. LUT-7G treatment also neutralizes the proliferative stimulus induced by the proinflammatory cytokines IL-22 and IL-6 in HEKn. Moreover, in the Imiquimod (IMQ) mouse model of psoriasis, topical administration of LUT-7G leads to a marked reduction of acanthosis and re-expression of epidermal differentiation markers. Dissection of the IL-22 signalling pathway, activated by IMQ treatment, demonstrates that LUT-7G impairs the nuclear translocation of phosphorylated (activated) STAT3, blocking the IL-22 signalling cascade. Thus LUT-7G appears to be a promising compound for the treatment of hyperproliferative and inflammatory skin diseases, such as psoriasis. |
format | Online Article Text |
id | pubmed-5108310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51083102016-11-15 Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model Palombo, R Savini, I Avigliano, L Madonna, S Cavani, A Albanesi, C Mauriello, A Melino, G Terrinoni, A Cell Death Dis Original Article The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result in pathological changes. Some common skin diseases, such as psoriasis, are characterized by hyperproliferation accompanied by inflammatory reactions, suggesting that molecules with topical anti-inflammatory and ROS scavenging abilities may be useful for their treatment. Here we investigate the potential of the flavone Luteolin-7-glucoside (LUT-7G) as a treatment for psoriasis. We show that LUT-7G leads to a modification of the cell cycle and the induction of keratinocyte differentiation, with modification of energy, fatty acid, and redox metabolism. LUT-7G treatment also neutralizes the proliferative stimulus induced by the proinflammatory cytokines IL-22 and IL-6 in HEKn. Moreover, in the Imiquimod (IMQ) mouse model of psoriasis, topical administration of LUT-7G leads to a marked reduction of acanthosis and re-expression of epidermal differentiation markers. Dissection of the IL-22 signalling pathway, activated by IMQ treatment, demonstrates that LUT-7G impairs the nuclear translocation of phosphorylated (activated) STAT3, blocking the IL-22 signalling cascade. Thus LUT-7G appears to be a promising compound for the treatment of hyperproliferative and inflammatory skin diseases, such as psoriasis. Nature Publishing Group 2016-08 2016-08-18 /pmc/articles/PMC5108310/ /pubmed/27537526 http://dx.doi.org/10.1038/cddis.2016.201 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Palombo, R Savini, I Avigliano, L Madonna, S Cavani, A Albanesi, C Mauriello, A Melino, G Terrinoni, A Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model |
title | Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model |
title_full | Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model |
title_fullStr | Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model |
title_full_unstemmed | Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model |
title_short | Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model |
title_sort | luteolin-7-glucoside inhibits il-22/stat3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108310/ https://www.ncbi.nlm.nih.gov/pubmed/27537526 http://dx.doi.org/10.1038/cddis.2016.201 |
work_keys_str_mv | AT palombor luteolin7glucosideinhibitsil22stat3pathwayreducingproliferationacanthosisandinflammationinkeratinocytesandinmousepsoriaticmodel AT savinii luteolin7glucosideinhibitsil22stat3pathwayreducingproliferationacanthosisandinflammationinkeratinocytesandinmousepsoriaticmodel AT aviglianol luteolin7glucosideinhibitsil22stat3pathwayreducingproliferationacanthosisandinflammationinkeratinocytesandinmousepsoriaticmodel AT madonnas luteolin7glucosideinhibitsil22stat3pathwayreducingproliferationacanthosisandinflammationinkeratinocytesandinmousepsoriaticmodel AT cavania luteolin7glucosideinhibitsil22stat3pathwayreducingproliferationacanthosisandinflammationinkeratinocytesandinmousepsoriaticmodel AT albanesic luteolin7glucosideinhibitsil22stat3pathwayreducingproliferationacanthosisandinflammationinkeratinocytesandinmousepsoriaticmodel AT maurielloa luteolin7glucosideinhibitsil22stat3pathwayreducingproliferationacanthosisandinflammationinkeratinocytesandinmousepsoriaticmodel AT melinog luteolin7glucosideinhibitsil22stat3pathwayreducingproliferationacanthosisandinflammationinkeratinocytesandinmousepsoriaticmodel AT terrinonia luteolin7glucosideinhibitsil22stat3pathwayreducingproliferationacanthosisandinflammationinkeratinocytesandinmousepsoriaticmodel |