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鉴定与人体皮肤模型经紫外线辐射相关的巨噬细胞。

Characterization of macrophages associated with human skin models exposed to UV radiation.

机构信息

Graduate Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.

Center of Excellence in Materials and Bio-interfaces, Chulalongkorn University, Bangkok, 10330, Thailand.

出版信息

Commun Biol. 2024 Oct 8;7(1):1284. doi: 10.1038/s42003-024-06975-z.

DOI:10.1038/s42003-024-06975-z
PMID:39379484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11461876/
Abstract

Skin macrophages play important roles in the response to external stimuli. Human skin equivalents (HSEs) incorporating the human monocytic cell line THP-1 were fabricated to generate immunocompetent human skin models. These HSEs were used to investigate the influence of the skin microenvironment and ultraviolet A (UVA) on macrophages. Transcriptomic analysis revealed that THP-1 cells in HSEs were enriched in extracellular matrix interaction hallmark but downregulated in DNA replication hallmark. Upon UVA exposure, immunocompetent HSEs presented epidermal distortion and increased DNA double-strand breaks (DSBs). The genes associated with oxidative stress and the inflammatory response were significantly upregulated in THP-1 cells. When the photoprotective agent mycosporine-2-glycine from cyanobacteria was applied to HSEs, the incidence of UVA-induced DSBs was significantly lower, and inflammatory and UV response hallmarks were downregulated in THP-1 cells. Taken together, these results suggest that immunocompetent HSEs can be used to investigate the responses of skin-resident macrophages to external stimuli.

摘要

皮肤巨噬细胞在对外界刺激的反应中发挥着重要作用。为了生成具有免疫活性的人类皮肤模型，我们构建了包含人单核细胞系 THP-1 的人类皮肤等效物（HSE）。我们使用这些 HSE 来研究皮肤微环境和紫外线 A（UVA）对巨噬细胞的影响。转录组分析显示，HSE 中的 THP-1 细胞富含细胞外基质相互作用特征，但 DNA 复制特征下调。在 UVA 暴露下，具有免疫活性的 HSE 呈现表皮扭曲和增加的 DNA 双链断裂（DSBs）。THP-1 细胞中与氧化应激和炎症反应相关的基因显著上调。当将来自蓝藻的光保护剂菌多酚-2-甘氨酸应用于 HSE 时，UVA 诱导的 DSBs 的发生率显著降低，THP-1 细胞中的炎症和 UV 反应特征下调。总之，这些结果表明，具有免疫活性的 HSE 可用于研究皮肤驻留巨噬细胞对外界刺激的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/c17268e35e9b/42003_2024_6975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/a951e5ce99c8/42003_2024_6975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/2bf59d8efef4/42003_2024_6975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/3fb314a40b82/42003_2024_6975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/f4c9afa21d7c/42003_2024_6975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/0fcc64a1f5b1/42003_2024_6975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/c17268e35e9b/42003_2024_6975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/a951e5ce99c8/42003_2024_6975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/2bf59d8efef4/42003_2024_6975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/3fb314a40b82/42003_2024_6975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/f4c9afa21d7c/42003_2024_6975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/0fcc64a1f5b1/42003_2024_6975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e4/11461876/c17268e35e9b/42003_2024_6975_Fig6_HTML.jpg

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