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Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation

The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 infla...

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Autores principales: Lee, Se-Bin, Kang, Ju-Hui, Sim, Eun-Jung, Jung, Ye-Rin, Kim, Jeong-Hyeon, Hillman, Prima F., Nam, Sang-Jip, Kang, Tae-Bong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051512/
https://www.ncbi.nlm.nih.gov/pubmed/36982727
http://dx.doi.org/10.3390/ijms24065653
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author Lee, Se-Bin
Kang, Ju-Hui
Sim, Eun-Jung
Jung, Ye-Rin
Kim, Jeong-Hyeon
Hillman, Prima F.
Nam, Sang-Jip
Kang, Tae-Bong
author_facet Lee, Se-Bin
Kang, Ju-Hui
Sim, Eun-Jung
Jung, Ye-Rin
Kim, Jeong-Hyeon
Hillman, Prima F.
Nam, Sang-Jip
Kang, Tae-Bong
author_sort Lee, Se-Bin
collection PubMed
description The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 inflammasome activation. In this study, we aimed to investigate the inhibitory activity of ethanolic extracts of seeds of Cornus officinalis (CO), a herb and food plant used in traditional medicine, on AIM2-inflammasome activation. We found that CO inhibited the release of IL-1β induced by dsDNA in both BMDMs and HaCaT cells, but that it showed no effect on the release of IL-1β induced by NLRP3 inflammasome triggers, such as nigericin and silica, or the NLRC4 inflammasome trigger flagellin. Furthermore, we demonstrated that CO inhibited the cleavage of caspase-1, an inflammasome activation marker, and an upstream event, the translocation and speck formation of ASC. In addition, further experiments and mechanistic investigations revealed that CO can inhibit AIM2 speck formation induced by dsDNA in AIM2-overexpressing HEK293T cells. To verify the correlation in vivo, we investigated the efficacy of CO in an imiquimod (IMQ)-induced psoriasis model, which has reported associations with the AIM2 inflammasome. We found that topical application of CO alleviated psoriasis-like symptoms, such as erythema, scaling, and epidermal thickening, in a dose-dependent manner. Moreover, CO also significantly decreased IMQ-induced expression of AIM2 inflammasome components, including AIM2, ASC, and caspase-1, and led to the elevation of serum IL-17A. In conclusion, our results suggest that CO may be a valuable candidate for the discovery of AIM2 inhibitors and the regulation of AIM2-related diseases.
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spelling pubmed-100515122023-03-30 Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation Lee, Se-Bin Kang, Ju-Hui Sim, Eun-Jung Jung, Ye-Rin Kim, Jeong-Hyeon Hillman, Prima F. Nam, Sang-Jip Kang, Tae-Bong Int J Mol Sci Article The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 inflammasome activation. In this study, we aimed to investigate the inhibitory activity of ethanolic extracts of seeds of Cornus officinalis (CO), a herb and food plant used in traditional medicine, on AIM2-inflammasome activation. We found that CO inhibited the release of IL-1β induced by dsDNA in both BMDMs and HaCaT cells, but that it showed no effect on the release of IL-1β induced by NLRP3 inflammasome triggers, such as nigericin and silica, or the NLRC4 inflammasome trigger flagellin. Furthermore, we demonstrated that CO inhibited the cleavage of caspase-1, an inflammasome activation marker, and an upstream event, the translocation and speck formation of ASC. In addition, further experiments and mechanistic investigations revealed that CO can inhibit AIM2 speck formation induced by dsDNA in AIM2-overexpressing HEK293T cells. To verify the correlation in vivo, we investigated the efficacy of CO in an imiquimod (IMQ)-induced psoriasis model, which has reported associations with the AIM2 inflammasome. We found that topical application of CO alleviated psoriasis-like symptoms, such as erythema, scaling, and epidermal thickening, in a dose-dependent manner. Moreover, CO also significantly decreased IMQ-induced expression of AIM2 inflammasome components, including AIM2, ASC, and caspase-1, and led to the elevation of serum IL-17A. In conclusion, our results suggest that CO may be a valuable candidate for the discovery of AIM2 inhibitors and the regulation of AIM2-related diseases. MDPI 2023-03-15 /pmc/articles/PMC10051512/ /pubmed/36982727 http://dx.doi.org/10.3390/ijms24065653 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
Lee, Se-Bin
Kang, Ju-Hui
Sim, Eun-Jung
Jung, Ye-Rin
Kim, Jeong-Hyeon
Hillman, Prima F.
Nam, Sang-Jip
Kang, Tae-Bong
Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation
title Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation
title_full Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation
title_fullStr Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation
title_full_unstemmed Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation
title_short Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation
title_sort cornus officinalis seed extract inhibits aim2-inflammasome activation and attenuates imiquimod-induced psoriasis-like skin inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051512/
https://www.ncbi.nlm.nih.gov/pubmed/36982727
http://dx.doi.org/10.3390/ijms24065653
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