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Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts
In autoimmune diseases, fibroblasts produce and secrete various cytokines and act as sentinel immune cells during inflammatory states. However, the contribution of sentinel immune cells (i.e. dermal fibroblasts) in autoimmune diseases of the skin, such as atopic dermatitis, has been obscure. The pro...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568182/ https://www.ncbi.nlm.nih.gov/pubmed/34735542 http://dx.doi.org/10.1371/journal.pone.0259489 |
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author | Naruke, Atsuto Nakano, Rei Nunomura, Junichi Suwabe, Yoko Nakano, Masumi Namba, Shinichi Kitanaka, Taku Kitanaka, Nanako Sugiya, Hiroshi Nakayama, Tomohiro |
author_facet | Naruke, Atsuto Nakano, Rei Nunomura, Junichi Suwabe, Yoko Nakano, Masumi Namba, Shinichi Kitanaka, Taku Kitanaka, Nanako Sugiya, Hiroshi Nakayama, Tomohiro |
author_sort | Naruke, Atsuto |
collection | PubMed |
description | In autoimmune diseases, fibroblasts produce and secrete various cytokines and act as sentinel immune cells during inflammatory states. However, the contribution of sentinel immune cells (i.e. dermal fibroblasts) in autoimmune diseases of the skin, such as atopic dermatitis, has been obscure. The pro-inflammatory cytokine interleukin 1β (IL-1β) induces the expression of chemokines, such as interleukin 8 (IL-8), in autoimmune diseases of the skin. IL-8 induces the activation and recruitment of innate immune cells such as neutrophils to the site of inflammation. IL-1β-mediated induction of IL-8 expression is important for the pathogenesis of autoimmune diseases; however, the intracellular singling remains to be understood. To elucidate the mechanism of the onset of autoimmune diseases, we established a model for IL-1β-induced dermatitis and investigated MAPK signaling pathways in IL-1β-induced IL-8 expression. We also identified that a MAP3K Tpl2 acts as an upstream modulator of IL-1β-induced ERK1/2 activation in dermal fibroblasts. We observed an increase in the expression of IL-8 mRNA and protein in cells treated with IL-1β. ERK1/2 inhibitors significantly reduced IL-1β-induced IL-8 expression, whereas the inhibitor for p38 MAPK or JNK had no effect. IL-1β induced ERK1/2 phosphorylation, which was attenuated in the presence of an ERK1/2 inhibitor. IL-1β failed to induce IL-8 expression in cells transfected with siRNA for ERK1, or ERK2. Notably, a Tpl2 inhibitor reduced IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. We confirmed that the silencing of Tpl2 in siRNA-transfected fibroblasts prevented both in IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. Taken together, our data indicate the importance of Tpl2 in the modulation of ERK1/2 signaling involved in the IL-1β-induced development of autoimmune diseases affecting the dermal tissue, such as atopic dermatitis. |
format | Online Article Text |
id | pubmed-8568182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-85681822021-11-05 Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts Naruke, Atsuto Nakano, Rei Nunomura, Junichi Suwabe, Yoko Nakano, Masumi Namba, Shinichi Kitanaka, Taku Kitanaka, Nanako Sugiya, Hiroshi Nakayama, Tomohiro PLoS One Research Article In autoimmune diseases, fibroblasts produce and secrete various cytokines and act as sentinel immune cells during inflammatory states. However, the contribution of sentinel immune cells (i.e. dermal fibroblasts) in autoimmune diseases of the skin, such as atopic dermatitis, has been obscure. The pro-inflammatory cytokine interleukin 1β (IL-1β) induces the expression of chemokines, such as interleukin 8 (IL-8), in autoimmune diseases of the skin. IL-8 induces the activation and recruitment of innate immune cells such as neutrophils to the site of inflammation. IL-1β-mediated induction of IL-8 expression is important for the pathogenesis of autoimmune diseases; however, the intracellular singling remains to be understood. To elucidate the mechanism of the onset of autoimmune diseases, we established a model for IL-1β-induced dermatitis and investigated MAPK signaling pathways in IL-1β-induced IL-8 expression. We also identified that a MAP3K Tpl2 acts as an upstream modulator of IL-1β-induced ERK1/2 activation in dermal fibroblasts. We observed an increase in the expression of IL-8 mRNA and protein in cells treated with IL-1β. ERK1/2 inhibitors significantly reduced IL-1β-induced IL-8 expression, whereas the inhibitor for p38 MAPK or JNK had no effect. IL-1β induced ERK1/2 phosphorylation, which was attenuated in the presence of an ERK1/2 inhibitor. IL-1β failed to induce IL-8 expression in cells transfected with siRNA for ERK1, or ERK2. Notably, a Tpl2 inhibitor reduced IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. We confirmed that the silencing of Tpl2 in siRNA-transfected fibroblasts prevented both in IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. Taken together, our data indicate the importance of Tpl2 in the modulation of ERK1/2 signaling involved in the IL-1β-induced development of autoimmune diseases affecting the dermal tissue, such as atopic dermatitis. Public Library of Science 2021-11-04 /pmc/articles/PMC8568182/ /pubmed/34735542 http://dx.doi.org/10.1371/journal.pone.0259489 Text en © 2021 Naruke et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Naruke, Atsuto Nakano, Rei Nunomura, Junichi Suwabe, Yoko Nakano, Masumi Namba, Shinichi Kitanaka, Taku Kitanaka, Nanako Sugiya, Hiroshi Nakayama, Tomohiro Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts |
title | Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts |
title_full | Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts |
title_fullStr | Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts |
title_full_unstemmed | Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts |
title_short | Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts |
title_sort | tpl2 contributes to il-1β-induced il-8 expression via erk1/2 activation in canine dermal fibroblasts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568182/ https://www.ncbi.nlm.nih.gov/pubmed/34735542 http://dx.doi.org/10.1371/journal.pone.0259489 |
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