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

Abstract

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.

Erythroid Differentiation Regulator 1 as a Novel Biomarker for Hair Loss Disorders

“…In this study, Erdr1 downregulation was found in both scarring alopecia and AA, consistent with results of previous studies, which show Erdr1 downregulation in chronic inflammatory disorders, such as psoriasis and rosacea [17,25]. This suggests that inflammation is related to Erdr1 downregulation in hair loss disorders.…”

“…In our previous study, we have observed negative correlations between IL-18 and erythroid differentiation regulator 1 (Erdr1) in human keratinocytes [16]. Recently, it has been reported that Erdr1 plays an important role in the inflammatory process via regulating the immune system in various cutaneous chronic inflammatory disorders, such as psoriasis and rosacea [16,17]. …”

Downregulation of erythroid differentiation regulator 1 (Erdr1) plays a critical role in psoriasis pathogenesis

“…As shown in Figure S3, recombinant Erdr1 decreased inflammatory cell infiltration and TNF‐ α production in psoriasis‐like skin inflammation in vivo mouse model. Additionally, our previous studies reported that rErdr1 reduces inflammatory cell infiltration and angiogenesis in rosacea and decreases migratory ability of cancer cells, further supporting the anti‐inflammatory effects of Erdr1 . In addition, we previously reported that Erdr1 exerts a proapoptotic effect in the human keratinocyte cell line, HaCaT, suggesting that Erdr1 may be a useful therapeutic target for psoriasis, which is characterized by low apoptosis in hyperproliferating keratinocytes .…”

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“…In addition, recent studies suggest the anti-inflammatory property of Erdr1 in contrast to the pro-inflammatory effects of IL-18. Treatment with rErdr1 has a therapeutic effect on rosacea, an inflammatory skin disease, via inhibition of angiogenesis and inflammatory cell infiltration [9]. In addition to improving rosacea, rErdr1 inhibits TNF-α production, inflammatory cell infiltration into lesional skin, and chemokine production in a representative inflammatory skin disease, psoriasis, further supporting an anti-inflammatory function of Erdr1 [6].…”