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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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