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米诺环素在体内和体外通过TLR4介导的NF-κB信号通路抑制酒渣鼻样炎症。

Minocycline inhibits rosacea-like inflammation through the TLR4-mediated NF-κB signaling pathway in vivo and in vitro.

作者信息

Hua Piyan, Tu Ying, Yang Zhenghui, He Yunting, He Li, Yao Qiuyan, Gu Hua

机构信息

Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.

出版信息

PLoS One. 2025 May 16;20(5):e0323598. doi: 10.1371/journal.pone.0323598. eCollection 2025.

DOI:10.1371/journal.pone.0323598
PMID:40378103
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12083832/
Abstract

BACKGROUND

Rosacea is a chronic inflammatory skin disease characterized by multiple intricate pathogenic factors. Previous studies have substantiated the anti-inflammatory properties of minocycline and its potential therapeutic efficacy in treating rosacea. However, further elucidation of the underlying mechanism is warranted.

METHODS

HaCaT cells and BALB/c mice were treated with LL37. Moreover, the effect of minocycline on rosacea was explored through the addition of an NF-κB inhibitor (PDTC) or overexpression of Toll-like receptor 4 (TLR4). The expression of related markers was detected by western blotting, immunofluorescence, ELISA, flow cytometry, etc.

RESULTS

Minocycline suppressed dermal infiltration of inflammatory cells in rosacea-like mice and reduced the expression of inflammatory cytokines in rosacea-like mice and cells. Moreover, minocycline downregulated the expression of TLR4 and p-NF-κB thereby inhibiting ROS production. However, overexpression of TLR4 or the addition of PDTC counteracted the effects of minocycline by promoting cellular inflammation and ROS production. Mechanistically, minocycline hinders TLR4/TNF-α activation induced by LL37 in skin and cells to suppress the expression of inflammatory cytokines.

CONCLUSION

Minocycline alleviates inflammation progression in rosacea by downregulating TLR4 and inhibiting the activation of the NF-κB pathway, providing a scientific basis for subsequent clinical treatment.

摘要

背景

酒渣鼻是一种慢性炎症性皮肤病,具有多种复杂的致病因素。先前的研究证实了米诺环素的抗炎特性及其在治疗酒渣鼻方面的潜在治疗效果。然而,有必要进一步阐明其潜在机制。

方法

用LL37处理HaCaT细胞和BALB/c小鼠。此外,通过添加NF-κB抑制剂(PDTC)或过表达Toll样受体4(TLR4)来探究米诺环素对酒渣鼻的影响。通过蛋白质免疫印迹法、免疫荧光法、酶联免疫吸附测定法、流式细胞术等检测相关标志物的表达。

结果

米诺环素抑制了酒渣鼻样小鼠真皮层炎性细胞浸润,并降低了酒渣鼻样小鼠和细胞中炎性细胞因子的表达。此外,米诺环素下调了TLR4和p-NF-κB的表达,从而抑制了活性氧的产生。然而,TLR4的过表达或PDTC的添加通过促进细胞炎症和活性氧的产生抵消了米诺环素的作用。从机制上讲,米诺环素阻碍了LL37在皮肤和细胞中诱导的TLR4/TNF-α激活,从而抑制炎性细胞因子的表达。

结论

米诺环素通过下调TLR4并抑制NF-κB通路的激活来减轻酒渣鼻的炎症进展,为后续临床治疗提供了科学依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/55c25fe8d9e6/pone.0323598.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/f4f26b6a6dda/pone.0323598.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/d28a6c78322c/pone.0323598.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/178ed502bf22/pone.0323598.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/30d24439adad/pone.0323598.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/37efd9d12e30/pone.0323598.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/55c25fe8d9e6/pone.0323598.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/f4f26b6a6dda/pone.0323598.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/d28a6c78322c/pone.0323598.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/178ed502bf22/pone.0323598.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/30d24439adad/pone.0323598.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/37efd9d12e30/pone.0323598.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c6/12083832/55c25fe8d9e6/pone.0323598.g006.jpg

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本文引用的文献

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2
Minocycline prevents photoreceptor degeneration in Retinitis pigmentosa through modulating mitochondrial homeostasis.米诺环素通过调节线粒体稳态预防色素性视网膜炎中的光感受器变性。
Int Immunopharmacol. 2024 Sep 30;139:112703. doi: 10.1016/j.intimp.2024.112703. Epub 2024 Jul 17.
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Minocycline induced apoptosis and suppressed expression of matrix metalloproteinases 2 and 9 in the breast cancer MCF-7 cells.
米诺环素诱导乳腺癌 MCF-7 细胞凋亡及下调基质金属蛋白酶 2 和 9 的表达。
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Dendrobium polysaccharide (DOP) ameliorates the LL-37-induced rosacea by inhibiting NF-κB activation in a mouse model.铁皮石斛多糖(DOP)通过抑制 NF-κB 激活改善 LL-37 诱导的小鼠酒渣鼻。
Skin Res Technol. 2024 Jan;30(1):e13543. doi: 10.1111/srt.13543.
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Biomarkers in rosacea: A systematic review.酒渣鼻的生物标志物:系统评价。
J Eur Acad Dermatol Venereol. 2024 Jun;38(6):1048-1057. doi: 10.1111/jdv.19732. Epub 2023 Dec 11.
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Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer's disease.小胶质细胞功能、INPP5D/SHIP1 信号通路和 NLRP3 炎性体激活:对阿尔茨海默病的影响。
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