Cargando…

CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis

CCN1, an extracellular protein also known as cysteine-rich protein 61 (Cyr61), is a novel pro-inflammatory factor involved in the pathogenesis of rheumatoid arthritis. As an inflammatory disease, psoriasis is characterized by keratinocyte activation-induced epidermal hyperplasia and cytokine-mediate...

Descripción completa

Detalles Bibliográficos
Autores principales: Sun, Yue, Zhang, Jie, Zhai, Tianhang, Li, Huidan, Li, Haichuan, Huo, Rongfen, Shen, Baihua, Wang, Beiqing, Chen, Xiangdong, Li, Ningli, Teng, Jialin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339692/
https://www.ncbi.nlm.nih.gov/pubmed/28266627
http://dx.doi.org/10.1038/srep43310
_version_ 1782512708078272512
author Sun, Yue
Zhang, Jie
Zhai, Tianhang
Li, Huidan
Li, Haichuan
Huo, Rongfen
Shen, Baihua
Wang, Beiqing
Chen, Xiangdong
Li, Ningli
Teng, Jialin
author_facet Sun, Yue
Zhang, Jie
Zhai, Tianhang
Li, Huidan
Li, Haichuan
Huo, Rongfen
Shen, Baihua
Wang, Beiqing
Chen, Xiangdong
Li, Ningli
Teng, Jialin
author_sort Sun, Yue
collection PubMed
description CCN1, an extracellular protein also known as cysteine-rich protein 61 (Cyr61), is a novel pro-inflammatory factor involved in the pathogenesis of rheumatoid arthritis. As an inflammatory disease, psoriasis is characterized by keratinocyte activation-induced epidermal hyperplasia and cytokine-mediated inflammation. We demonstrated in our previous study that CCN1 promoted keratinocyte activation in psoriasis. However, the role of CCN1 in regulating inflammation in psoriasis is still unknown. Here, we showed that CCN1 increased inflammatory cytokine IL-1β production in keratinocytes. Furthermore, endogenous ATP and caspase-1 were required for mature IL-1β production stimulated by CCN1 in keratinocytes. After binding to the receptor of integrin α6β1, CCN1 activated the downstream p38 MAPK signaling pathway, thus inducing the expression of IL-1β. In addition, we inhibited CCN1 function in mouse models of psoriasis, and decreased IL-1β production was observed in vivo. Overall, we showed that CCN1 increased IL-1β production via p38 MAPK signaling, indicating a role for CCN1 protein in regulating inflammation in psoriasis.
format Online
Article
Text
id pubmed-5339692
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-53396922017-03-10 CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis Sun, Yue Zhang, Jie Zhai, Tianhang Li, Huidan Li, Haichuan Huo, Rongfen Shen, Baihua Wang, Beiqing Chen, Xiangdong Li, Ningli Teng, Jialin Sci Rep Article CCN1, an extracellular protein also known as cysteine-rich protein 61 (Cyr61), is a novel pro-inflammatory factor involved in the pathogenesis of rheumatoid arthritis. As an inflammatory disease, psoriasis is characterized by keratinocyte activation-induced epidermal hyperplasia and cytokine-mediated inflammation. We demonstrated in our previous study that CCN1 promoted keratinocyte activation in psoriasis. However, the role of CCN1 in regulating inflammation in psoriasis is still unknown. Here, we showed that CCN1 increased inflammatory cytokine IL-1β production in keratinocytes. Furthermore, endogenous ATP and caspase-1 were required for mature IL-1β production stimulated by CCN1 in keratinocytes. After binding to the receptor of integrin α6β1, CCN1 activated the downstream p38 MAPK signaling pathway, thus inducing the expression of IL-1β. In addition, we inhibited CCN1 function in mouse models of psoriasis, and decreased IL-1β production was observed in vivo. Overall, we showed that CCN1 increased IL-1β production via p38 MAPK signaling, indicating a role for CCN1 protein in regulating inflammation in psoriasis. Nature Publishing Group 2017-03-07 /pmc/articles/PMC5339692/ /pubmed/28266627 http://dx.doi.org/10.1038/srep43310 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ 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 Article
Sun, Yue
Zhang, Jie
Zhai, Tianhang
Li, Huidan
Li, Haichuan
Huo, Rongfen
Shen, Baihua
Wang, Beiqing
Chen, Xiangdong
Li, Ningli
Teng, Jialin
CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis
title CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis
title_full CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis
title_fullStr CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis
title_full_unstemmed CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis
title_short CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psoriasis
title_sort ccn1 promotes il-1β production in keratinocytes by activating p38 mapk signaling in psoriasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339692/
https://www.ncbi.nlm.nih.gov/pubmed/28266627
http://dx.doi.org/10.1038/srep43310
work_keys_str_mv AT sunyue ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT zhangjie ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT zhaitianhang ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT lihuidan ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT lihaichuan ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT huorongfen ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT shenbaihua ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT wangbeiqing ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT chenxiangdong ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT liningli ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis
AT tengjialin ccn1promotesil1bproductioninkeratinocytesbyactivatingp38mapksignalinginpsoriasis