Long-pulsed 1064-nm Nd: YAG laser ameliorates LL-37-induced rosacea-like skin lesions through promoting collagen remodeling in BALB/c mice.

Long-pulsed 1064-nm neodymium: yttrium-aluminum-garnet laser (LPND) effectively treats rosacea, although the underlying mechanism is unclear, to evaluate the histological effects and molecular mechanism of LPND on LL-37-induced rosacea-like skin lesions in mice. Intradermal injection of LL-37 was performed into the dorsal skin of BALB/c mice (n = 30) twice a day for 2 days. Fifteen mice were treated with LPND. After 48 h, the excised skin sample was stained for histology and type I collagen; transforming growth factor (TGF)-ß, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase (TIMP)-1, tumor necrosis factor (TNF)-α, and interleukin (IL)-1α mRNA levels were determined by real-time RT-PCR. Intradermal injection of LL-37 induced rosacea-like clinical features. LPND treatment significantly reduced erythema and increased dermal collagen production. Levels of Type I collagen, TGF-ß, and MMP-1 mRNA were significantly higher in LPND-treated mice than in untreated mice. LPND may improve rosacea by ameliorating dermal connective tissue disorganization and elastosis through MMP-mediated dermal collagen remodeling.

Inhibition of mast cell infiltration in an LL-37-induced rosacea mouse model using topical brimonidine tartrate 0.33% gel.

Brimonidine is a highly selective α2-adrenergic receptor agonist approved by the FDA for the treatment of rosacea. Rosacea is a major clinical disease with vasodilatation and rash on the centre of the face, and that brimonidine as a vasoconstrictor can act as a remedy for rosacea. However, there is no study of how brimonidine has an effect on rosacea-related immune cells or mechanisms in the skin to improve rosacea. In this study, we observed that clinical features of rosacea induced by LL-37 in Balb/c mice were improved after the application of brimonidine gel, and we also showed a marked decrease in the number of inflammatory cells, especially mast cells (MCs) histologically. Furthermore, we confirmed that mRNA levels of MC enzymes increased by LL-37 were reduced by brimonidine gel. To our knowledge, we first found that brimonidine has a mechanism of treating rosacea by reducing the number and mRNA levels of MC-specific enzymes, an important immune cell in the pathogenesis of rosacea.

Recombinant erythroid differentiation regulator 1 inhibits both inflammation and angiogenesis in a mouse model of rosacea.

The erythroid differentiation regulator 1 (Erdr1), which is a novel and highly conserved factor, was recently reported to be negatively regulated by IL-18 and to play a crucial role as an antimetastatic factor. IL-18 is a proinflammatory cytokine that functions as an angiogenic mediator in inflammation. Rosacea is a chronic inflammatory skin disorder that is characterized by abnormal inflammation and vascular hyperactivity of the facial skin. To determine whether Erdr1 contributes to the regulation of the chronic inflammatory process in the development of rosacea, an immunohistochemical analysis was performed in healthy donors and patients with rosacea. In this study, we showed that Erdr1 was downregulated, whereas IL-18 was upregulated, in patients with rosacea, which led us to question the role of Erdr1 in this disorder. Moreover, a rosacea-like BALB/c mouse model was used to determine the role of Erdr1 in rosacea in vivo. LL-37 injection induced typical rosacea features, including erythema, telangiectasia and inflammation. Treatment with recombinant Erdr1 (rErdr1) resulted in a significant reduction of erythema, inflammatory cell infiltration (including CD4(+) and CD8(+) T cells), and microvessel density with vascular endothelial growth factor (VEGF). Taken together, our findings suggest that rErdr1 may be involved in attenuating the inflammation and angiogenesis associated with the pathogenesis of rosacea. Thus, these results provide new insight into the mechanism involved in this condition and indicate that rErdr1 could be a potential target for therapeutic intervention of rosacea.

Effects of the Ultra-High-Frequency Electrical Field Radiofrequency Device on Mouse Skin: A Histologic and Molecular Study.

BACKGROUND: Radiofrequency technology is one of the most recently developed methods for noninvasive skin tightening and facial contouring, and works by generating thermal energy in the deep dermis. Although clinical improvements have been reported using radiofrequency devices, there are few histologic and molecular studies about the mechanisms of dermal collagen remodeling. The authors investigated the histologic effects of an ultra-high-frequency electrical field (40.68 MHz) radiofrequency device (Polargen) on collagen remodeling in hairless mouse skin and evaluated its relative molecular mechanism. METHODS: The radiofrequency was applied to the dorsal skin of hairless mice three times per week for 2 weeks. At 21 days after initial treatment, treated skin and nontreated control skin samples were excised for semiquantitative analysis of histologic features, including collagen. The authors also checked the mRNA expression levels of collagen type 1, transforming growth factor (TGF)-ß, matrix metalloproteinase-1, vascular endothelial growth factor, tumor necrosis factor-α, and interleukin-1. RESULTS: Histologic examination revealed epidermal hyperplasia, increased collagen staining, and fat atrophy in treated skin area compared with the nontreated skin area. In addition, mRNA expression of collagen type І, TGF-ß, and vascular endothelial growth factor in radiofrequency-treated areas was significantly increased compared with that in untreated control areas (p < 0.05, p < 0.05, and p < 0.01, respectively). CONCLUSIONS: These results suggest that the device may facilitate replacement of subcutaneous fat tissue with new collagen in association with the increased mRNA levels in TGF-ß and vascular endothelial growth factor. Therefore, this device may effectively reduce adipose tissue and achieve facial contouring in addition to skin tightening.