Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Yumeng Kang; Chuanxi Zhang; Yang He; Ziyan Zhang; Heliang Liu; Zhongqiu Wei; Jie Yang

doi:10.2147/DDDT.S393122

Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Drug Des Devel Ther. 2022 Dec 2:16:4127-4138. doi: 10.2147/DDDT.S393122. eCollection 2022.

Authors

Yumeng Kang¹, Chuanxi Zhang¹, Yang He¹, Ziyan Zhang¹, Heliang Liu², Zhongqiu Wei³, Jie Yang¹

Affiliations

¹ Department of Dermatology, Affiliated Hospital of North China University of Science and Technology, Tangshan, People's Republic of China.
² Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North China University of Science and Technology, Tangshan, People's Republic of China.
³ School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, People's Republic of China.

Abstract

Purpose: Most of the existing studies focus on the early inflammation of rosacea, with few interventions on the later development of fibrosis and the relationship between thalidomide and rosacea. The purpose of this study was to construct a long-term induction model and explore the effects of thalidomide on the later stage of inflammation and early stage of fibrosis in rosacea.

Patients and methods: BALB/c male mice were randomly divided into four groups: control group, control plus thalidomide group, LL-37 group and LL-37 plus thalidomide group, Intradermal and intraperitoneal injections were given. After repeated induction, skin changes were recorded by taking photos. The animals were sacrificed, the back skin was used for HE staining and VG staining to detect histomorphological characteristics. Immunofluorescence staining and Western blot were used to detect the expression of inflammatory and fibrosis-related factors.

Results: The results were compared with the early stage of the model, wherein the skin inflammation of the 20-day mice was more obvious with a trend of fibrosis. Compared with the control group, histopathological examination showed that the inflammatory cell infiltration in the LL-37 group was significantly increased, and the skin was thickened with collagen deposition. LL-37 induction significantly increased the expression of inflammatory markers (eg, TNF-α and IL-1β) and fibrotic markers (eg, COL1, α-SMA, vimentin and N-Cadherin). Intervention with thalidomide significantly reduced erythema, inflammatory cell infiltration, collagen deposition, and down-regulate the expression of inflammation and fibrosis related factors in rosacea mice.

Conclusion: The long-term continuous induction of LL-37 in mice could simulate the occurrence and development of rosacea, and thalidomide could ameliorate the rosacea induced by long-term exposure to LL-37 by regulating inflammatory infiltration, collagen deposition and fibrosis-related processes.

Keywords: LL-37; inflammation; rosacea; skin fibrosis; thalidomide.

MeSH terms

Animals
Collagen*
Fibrosis
Male
Mice
Thalidomide* / pharmacology
Thalidomide* / therapeutic use

Substances

Thalidomide
Collagen

Grants and funding

This work was funded by the National Natural Science Foundation of China (82204006), the Natural Science Foundation of Hebei Province (2022209039), Hebei Provincial Department of Education Project (QN2022007).