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Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F
The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as p...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049365/ https://www.ncbi.nlm.nih.gov/pubmed/36982506 http://dx.doi.org/10.3390/ijms24065434 |
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author | Nakanishi, Takehisa Iida, Shohei Maruyama, Junko Urushima, Hayato Ichishi, Masako Matsushima, Yoshiaki Mizutani, Kento Nakayama, Yuichi Sugioka, Kyoko Nishimura, Mai Umaoka, Ai Iwakura, Yoichiro Kondo, Makoto Habe, Koji Tsuruta, Daisuke Yamamoto, Osamu Imai, Yasutomo Yamanaka, Keiichi |
author_facet | Nakanishi, Takehisa Iida, Shohei Maruyama, Junko Urushima, Hayato Ichishi, Masako Matsushima, Yoshiaki Mizutani, Kento Nakayama, Yuichi Sugioka, Kyoko Nishimura, Mai Umaoka, Ai Iwakura, Yoichiro Kondo, Makoto Habe, Koji Tsuruta, Daisuke Yamamoto, Osamu Imai, Yasutomo Yamanaka, Keiichi |
author_sort | Nakanishi, Takehisa |
collection | PubMed |
description | The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as psoriasis and atopic dermatitis has received increasing attention, and vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. However, the detailed mechanism of arteriosclerosis in dermatitis and the role of cytokines have not been clarified so far. In the current study, using a spontaneous dermatitis model, we investigated the pathophysiology of arteriosclerosis and the treatment option for inflammatory skin conditions. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (Kcasp1Tg). The thoracic and abdominal aorta was investigated histologically. GeneChip and RT-PCR analysis were performed to measure the changes in mRNA levels in the aorta. To elucidate the direct effect on the artery by major inflammatory cytokines, endothelial cells, vascular smooth muscle cells, and fibroblast cells were co-cultured with several cytokines, and mRNA expression levels were measured. In order to observe the efficacy of IL-17A/F in arteriosclerosis, cross-mating with IL-17A, IL-17F, and IL-17A/F deficient mice was performed. Finally, we also measured snap tension in the abdominal aorta in WT, Kcasp1Tg, and IL17A/F-deficient mice. Kcasp1Tg showed a decrease in the diameter of the abdominal aorta compared to wild-type mice. mRNA levels for six genes including Apol11b, Camp, Chil3, S100a8, S100a9, and Spta1 were increased in the abdominal aorta of Kcasp1Tg. Some of the above mRNA levels were also increased in the co-culture with major inflammatory cytokines, IL-17A/F, IL-1β, and TNF-α. Dermatitis improved and mRNA levels were partially ameliorated in Kcasp1Tg with IL-17A/F deletion. Arterial fragility was also evidenced in the inflammatory model, but arterial flexibility was revealed in the IL-17A/F deletion model. Severe dermatitis is closely related to secondary arteriosclerosis caused by the persistent release of inflammatory cytokines. The results also proved that treatment against IL-17A and F may ameliorate arteriosclerosis. |
format | Online Article Text |
id | pubmed-10049365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100493652023-03-29 Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F Nakanishi, Takehisa Iida, Shohei Maruyama, Junko Urushima, Hayato Ichishi, Masako Matsushima, Yoshiaki Mizutani, Kento Nakayama, Yuichi Sugioka, Kyoko Nishimura, Mai Umaoka, Ai Iwakura, Yoichiro Kondo, Makoto Habe, Koji Tsuruta, Daisuke Yamamoto, Osamu Imai, Yasutomo Yamanaka, Keiichi Int J Mol Sci Article The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as psoriasis and atopic dermatitis has received increasing attention, and vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. However, the detailed mechanism of arteriosclerosis in dermatitis and the role of cytokines have not been clarified so far. In the current study, using a spontaneous dermatitis model, we investigated the pathophysiology of arteriosclerosis and the treatment option for inflammatory skin conditions. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (Kcasp1Tg). The thoracic and abdominal aorta was investigated histologically. GeneChip and RT-PCR analysis were performed to measure the changes in mRNA levels in the aorta. To elucidate the direct effect on the artery by major inflammatory cytokines, endothelial cells, vascular smooth muscle cells, and fibroblast cells were co-cultured with several cytokines, and mRNA expression levels were measured. In order to observe the efficacy of IL-17A/F in arteriosclerosis, cross-mating with IL-17A, IL-17F, and IL-17A/F deficient mice was performed. Finally, we also measured snap tension in the abdominal aorta in WT, Kcasp1Tg, and IL17A/F-deficient mice. Kcasp1Tg showed a decrease in the diameter of the abdominal aorta compared to wild-type mice. mRNA levels for six genes including Apol11b, Camp, Chil3, S100a8, S100a9, and Spta1 were increased in the abdominal aorta of Kcasp1Tg. Some of the above mRNA levels were also increased in the co-culture with major inflammatory cytokines, IL-17A/F, IL-1β, and TNF-α. Dermatitis improved and mRNA levels were partially ameliorated in Kcasp1Tg with IL-17A/F deletion. Arterial fragility was also evidenced in the inflammatory model, but arterial flexibility was revealed in the IL-17A/F deletion model. Severe dermatitis is closely related to secondary arteriosclerosis caused by the persistent release of inflammatory cytokines. The results also proved that treatment against IL-17A and F may ameliorate arteriosclerosis. MDPI 2023-03-12 /pmc/articles/PMC10049365/ /pubmed/36982506 http://dx.doi.org/10.3390/ijms24065434 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nakanishi, Takehisa Iida, Shohei Maruyama, Junko Urushima, Hayato Ichishi, Masako Matsushima, Yoshiaki Mizutani, Kento Nakayama, Yuichi Sugioka, Kyoko Nishimura, Mai Umaoka, Ai Iwakura, Yoichiro Kondo, Makoto Habe, Koji Tsuruta, Daisuke Yamamoto, Osamu Imai, Yasutomo Yamanaka, Keiichi Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F |
title | Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F |
title_full | Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F |
title_fullStr | Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F |
title_full_unstemmed | Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F |
title_short | Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F |
title_sort | arteriosclerosis derived from cutaneous inflammation is ameliorated by the deletion of il-17a and il-17f |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049365/ https://www.ncbi.nlm.nih.gov/pubmed/36982506 http://dx.doi.org/10.3390/ijms24065434 |
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