Abstract
Rosacea is a chronic facial inflammatory skin disease that occurs with dysfunction of the immune system. Colchicine was reported to have anti-inflammatory properties. However, the impact of colchicine on rosacea remains unclear. In the present study, the phenotype of rosacea lesions was evaluated by the redness score, inflammatory biomarkers were analyzed by reverse transcription PCR (RT‒PCR), and the infiltration of inflammatory cells was assessed by IHC analysis and immunofluorescence in a rosacea-like mouse model. In vitro, RT‒PCR was used to identify the inflammatory factors that Toll-like receptor 2 (TLR2) agonist caused neutrophils to produce, and immunofluorescence and coimmunoprecipitation were used to identify putative signalling pathways. We found that skin erythema and histopathological alterations, as well as elevated proinflammatory factors (IL-1β, IL-6, TNFα, CXCL2) and CAMP, were significantly ameliorated by colchicine treatment in LL37-induced rosacea-like mice. In addition, colchicine reduced the colocalization of TLR2 and neutrophils and the formation of neutrophil extracellular trap networks (NET) in mouse lesions. In neutrophils, colchicine markedly reduced TLR2 agonist-induced inflammatory biomarker expression, NET formation, and ROS production. Moreover, we found that LL37 could bind to TLR2 upon activation of TLR2 in neutrophils. Importantly, colchicine could repress the combination of TLR2 and LL37 in vivo. Finally, bioinformatics methods further validated the key molecules of neutrophil-related inflammation in rosacea, which is consistent with our experimental findings. Collectively, colchicine ameliorated rosacea-like dermatitis by regulating the neutrophil immune response activated by the TLR2 pathway, indicating that it could be an effective therapeutic option for patients with rosacea.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was supported by Guizhou Provincial Science and Technology Projects, ZK[2021] general 421. Guizhou Provincial Science and Technology Projects, ZK[2022] general 250. Fund for Less Developed Regions of the National Natural Science Foundation of China, (Grant: 82160601, GPPH-NSFC-2021-13)
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Xin Yuan and Chengxiang Lian designed research; Xin Yuan, Chengxiang Lian, Liang Sheng, and Guang Shi performed research; Leiwei Jiang contributed new reagents or analytic tools; Leiwei Jiang and Xin Yuan analyzed data; Chengxiang Lian and Xin Yuan wrote the paper.
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Yuan, X., Sheng, L., Shi, G. et al. Colchicine Alleviates Rosacea by Inhibiting Neutrophil Inflammation Activated by the TLR2 Pathway. Inflammation (2024). https://doi.org/10.1007/s10753-023-01956-6
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DOI: https://doi.org/10.1007/s10753-023-01956-6