Blue Light Irradiation Induces Human Keratinocyte Cell Damage via Transient Receptor Potential Vanilloid 1 (TRPV1) Regulation

Abstract

Although blue light has been reported to affect skin cells negatively, little is known about its action mechanisms in skin cells. Therefore, we investigated the role of the transient receptor potential vanilloid 1 (TRPV1) in blue light-induced effects on human keratinocytes and its underlying mechanisms. Blue light decreased cell proliferation and upregulated TRPV1 expression. Blue light also suppressed the epidermal growth factor receptor- (EGFR-) mediated signaling pathway by reducing the protein levels of EGFR and suppressing the EGFR/PI3K/AKT/GSK3β/FoxO3a pathway. The blue light-induced effect in cell proliferation was reversed by TRPV1 siRNA, but not capsazepine, a TRPV1-specific antagonist. In addition, blue light irradiation increased the production of reactive oxygen species (ROS) and tumor necrosis factor-α (TNF-α). Blue light irradiation also increased both phosphorylation levels of TRPV1 and calcium influx. The blue light-induced increase in production of ROS and TNF-α was reversed by capsazepine. Furthermore, the blue light-induced increase in production of TNF-α was attenuated by SP600125 or PDTC. These findings show that blue light regulates cell survival and production of ROS and TNF-α; its effects are mediated via TRPV1. Specifically, the effects of blue light on cell proliferation are mediated by upregulating TRPV1, a negative regulator of EGFR-FoxO3a signaling. Blue light-induced production of ROS and TNF-α is also mediated through increased calcium influx via TRPV1 activation.

Blue Light in Dermatology

“…It affects not only various signaling pathways, but also increases the level of pro-inflammatory cytokines and differentiation, and reduces proliferation. The authors demonstrated that the increase of TRPV1 caused EGFR destruction, which led to the inhibition of AKT/GSK3β/FoxO3a signaling, and in the end to the decrease of keratinocytes proliferation [ 25 ]. Thus, the main theory is that blue light via chromophores has an impact on proliferation and differentiation [ 23 ].…”

“…Similarly, Yoo et al demonstrated that blue light caused a rise of ROS release, which was dependent on transient receptor potential vanilloid 1 (TRPV1). They also found that blue light increased proinflammatory cytokine TNF-α production by activating of activator protein 1 (AP-1) and nuclear factor κB (NF-κB) [ 25 ]. In the study investigating the ROS formation following phototherapy, Nakashima et al found that blue light caused oxidative stress in human keratinocytes.…”

Aspergillus oryzae-Fermented Wheat Peptone Enhances the Potential of Proliferation and Hydration of Human Keratinocytes through Activation of p44/42 MAPK

“…The maintenance of an appropriate moisture content in the SC contributes to SC maturation and skin desquamation [ 25 ]. On the contrary, abnormally increased TEWL impairs various enzymatic activities required for normal barrier formation and desquamation, leading to accelerated skin aging and induction of skin diseases [ 26 ]. Therefore, maintenance of proper water content in the keratinocyte is essential for normal skin homeostasis.…”

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“…Immunocytochemistry analysis was conducted as previously described [ 25 ]. Specifically, while for fixation, cells were treated with 4% paraformaldehyde in PBS for 15 min, they were incubated with 0.1% Triton X-100 and 0.01% Tween-20 for 20 min at room temperature for the permeabilization.…”

“…Real-time polymerase chain reaction (RT-PCR) analysis was conducted as previously described [ 25 ]. Specifically, RT-PCR analysis was done with an ABI7900HT Instrument (Applied Biosystems, Waltham, MA, USA).…”