590 nm LED Irradiation Improved Erythema through Inhibiting Angiogenesis of Human Microvascular Endothelial Cells and Ameliorated Pigmentation in Melasma.

Melasma is a common refractory acquired pigmentary skin disease that mainly affects middle-aged women. The pathogenesis of melasma is still uncertain, while abnormal vascular endothelial cells may play a role. We previously demonstrated the yellow light of light-emitting diodes (LED) could inhibit melanogenesis through the photobiomodulation (PBM) of melanocytes and keratinocytes. In the current study, we investigated the effect of 590 nm LED on the function of human microvascular endothelial cells (HMEC-1). We revealed 0-40 J/cm2 590 nm LED had no toxic effect on HMEC-1 in vitro. 590 nm LED irradiation significantly reduced cell migration, tube formation, as well as the expression of vascular endothelial growth factor (VEGF) and stem cell factor (SCF), a pro-melanogenic factor. Moreover, we illustrated that 590 nm LED inhibited the phosphorylation of the AKT/PI3K/mTOR signaling pathway, and the inhibitory effect on HMEC-1 could be partially reversed by insulin-like growth factor 1 (IGF-1), an AKT/PI3K/mTOR pathway agonist. Besides, we conducted a pilot clinical study and observed a marked improvement on facial erythema and pigmentation in melasma patients after amber LED phototherapy. Taken together, 590 nm LED inhibited HMEC-1 migration, tube formation and the secretion of VEGF and SCF, predominantly through the inhibition of the AKT/PI3K/mTOR pathway, which may serve as a novel therapeutic option for melasma.

585 nm light-emitting diodes inhibit melanogenesis through upregulating H19/miR-675 axis in LEDs-irradiated keratinocytes by paracrine effect.

BACKGROUND: 585 nm light-emitting diodes have been proven to suppress melanogenesis in melanocytes. However, whether LEDs will influence normal human epidermal keratinocytes (NHEKs) and paracrine effect of LEDs-irradiated NHEKs in melanogenesis remains unknown. OBJECTIVE: To elucidate the possible mechanisms in vitro of anti-melanogenic activity of 585 nm LEDs on paracrine effect of NHEKs and its exosomes. METHODS: NHEKs irradiated with different fluences of 585 nm LEDs were evaluated the cell viability by CCK8 assay. Irradiated medium of NHEKs was co-cultured with melanocytes. Melanin content, tyrosinase activity and melanogenic enzymes activities were detected. Exosomes from NHEKs medium were isolated and characterized by electron microscopy and nanoparticle tracking analysis. The expression changes of H19 and its encoded exosomal miR-675 were analyzed. RESULTS: Irradiation with 585 nm LEDs from 0 J/cm2 to 20 J/cm2 had no cytotoxic effect on NHEKs. After co-cultured with irradiated medium of NHEKs, melanin content and tyrosinase activity were reduced and the melanogenic activities were downregulated on both mRNA and protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1). H19 and its derived exosomal miR-675 from NHEKs, which has been proven relevant to melanogenesis, were significantly upregulated after irradiation. Furthermore, H19 knockdown and miR-675 inhibition in NHEKs could attenuate the inhibition effect of 585 nm LEDs on melanogenesis. CONCLUSIONS: This study demonstrated that 585 nm LEDs could inhibit melanogenesis via the up-regulation of H19 and its derived exosomal miR-675 from NHEKs, which was considered as a novel paracrine factor in regulating melanogenesis.