Lithocholic acid promotes rosacea-like skin inflammation via G protein-coupled bile acid receptor 1

Kang

et al. 2023

CIMB

Rosacea is a chronic inflammatory skin disease whose late manifestations have not yet been clearly reported in animal models. The objective of this study is to describe the skin lesions and major histopathological changes in a rosacea-like phenotype in mice induced by prolonged LL-37 administration and furthermore, to assess the potential of long-term LL-37 administration in inducing irreversible rosacea-like skin lesion models. Balb/c mice were continuously injected intradermally with LL-37 every 12 h to induce a rosacea-like phenotype. After LL-37 injections were administered for 20 consecutive days, the area of rosacea-like lesions gradually expanded in the first 13 days, then entered a stable phase. Haematoxylin and eosin (H&E) and Van Gieson’s staining showed a high degree of inflammatory cell aggregation, thickening of the epidermis and dermis, and collagen deposition in large quantities. The results of immunofluorescence staining and Western blotting showed that the expression of α-SMA, TNF-α, vimentin, and COL1 in the skin of mice was significantly upregulated. Short-term LL-37 administration induced rosacea-like lesions that only featured the aggregation of inflammatory factors and thickening of the epidermis, whereas no collagen hyperplasia was observed, and a full recovery was noticed. However, rosacea-like skin lesions induced by long-term LL-37 administration did not completely recover. Our study compares rosacea-like lesions induced by short-term versus long-term LL-37 administration, and the results suggest that irreversible rosacea-like lesions can be induced by long-term LL-37 administration.

Section: Discussionmentioning

confidence: 99%

Long-Term Administration of LL-37 Can Induce Irreversible Rosacea-like Lesion

Kang

et al. 2023

CIMB

“…The study also found increased levels of glutamic acid and aspartic acid, which promote the production of NPs and NO, leading to erythema and capillary dilation [66]. Another study showed that rosacea patients have distinct levels of bile acids, including elevated lithocholic acid, which can stimulate the production of inflammatory cytokines and chemokines via activation of the G protein-coupled bile acid receptor 1 (GP-BAR1) [130]. Hypercholesterolemia has also been implicated in inflammation, as it leads to cholesterol accumulation in various immune cells, amplifying TLR signaling.…”

Section: Metabolic Dysfunctionmentioning

confidence: 94%

Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

Chen,

Wang,

Zhang

et al. 2023

Preprint

Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in-depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments.

“…The study also found increased levels of glutamic acid and aspartic acid, which promote the production of NPs and NO, leading to erythema and capillary dilation [ 66 ]. Another study showed that rosacea patients have distinct levels of bile acids, including elevated lithocholic acid, which can stimulate the production of inflammatory cytokines and chemokines via activation of the G protein-coupled bile acid receptor 1 (GPBAR1) [ 130 ]. Hypercholesterolemia has also been implicated in inflammation, as it leads to cholesterol accumulation in various immune cells, amplifying TLR signaling.…”

Section: Pathogenesismentioning

confidence: 99%

Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates

Chen,

Wang,

Zhang

et al. 2023

Biomedicines

Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments.