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.

Menopausal status is associated with weight gain, increased central fat mass, abnormal lipid metabolism, insulin resistance and susceptibility to metabolic syndrome (MetS). Leptin is synthesised and secreted by adipocytes. Serum leptin levels are highly correlated with fat mass. We determined the association between MetS and serum leptin levels in 153 postmenopausal women. The difference in serum leptin level between MetS and non-MetS groups showed a statistical significance after adjusting for body mass index (BMI; 19.9 ± 9.5 vs 12.1 ± 5.9 ng/ml, p = 0.013). The indicator of abdominal obesity, waist-to-hip ratio (WHR) and visceral fat area (VFA), had a positive correlation with serum leptin level in non-obese subjects after adjusting for BMI (p = 0.017, p < 0.001, respectively). Of the components of MetS, abdominal obesity and the number of MetS components had a positive correlation with serum leptin level (p < 0.05, p < 0.001, respectively).

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. | BACKGROUNDRosacea is a common chronic inflammatory skin disease characterized by telangiectasia and flushing.[1] The erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity in the central part of the face. Brimonidine tartrate 0.33% gel (Mirvaso gel; Galderma, Lausanne, Switzerland), a highly selective α2-adrenergic receptor agonist, was recently recommended for the treatment of persistent facial erythema in patients with rosacea due to its potent vasoconstrictive effects. [2] Several clinical studies have demonstrated that brimonidine rapidly improves facial flushing and erythema. [2,3] However, the molecular and histological effects of brimonidine on rosacea remain largely unknown. Although the vasoconstrictive property of brimonidine gel has been suggested to contribute to the therapeutic effect, it was assumed that not only contracting the expanded blood vessels would act on the therapeutic mechanism. | QUESTION ADDRESSEDThe aims of this study were to investigate the histological changes and gene expression levels in rosacea-like skin lesions when applied with brimonidine and to identify the role of brimonidine gel in the pathogenesis of rosacea. In this study, we investigated whether brimonidine gel could influence the number of mast cells (MCs) and mRnA levels of tryptase and chymase by evaluating the response of topical application of brimonidine gel to rosacea-like skin lesions in mice. | EXPERIMENTAL DESIGNThirty-five 7-week-old female Balb/c mice were used in this study (Dooyeol Biotech, Seoul, Korea). The experimental protocol was approved by the Animal Care Committee of Catholic University of Korea. The mice were divided into three groups: control (n=11), LL-37 (n=12), and LL-37 plus brimonidine (LL-37+ brimonidine; n=12). The mice in the LL-37 and LL-37+ brimonidine groups had LL-37 injected intradermally into shaved back skin to induce rosacea-like skin lesions.Immediately after the injection of LL-37 (40 μL), the mice in the LL-37+ brimonidine group had brimonidine tartrate 0.3...