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.