Pivotal roles of TRPV1 channel and Nrf2 factor in green light modulation of keratinocyte inflammatory response

Abstract

ABSTRACT: Photobiomodulation (PBM) is emerging as a promising non-invasive approach for managing inflammatory skin conditions. However, its precise molecular mechanisms, especially within the green light spectrum, remain elusive. In this study, we investigated the anti-inflammatory mechanisms of 520 nm green light in primary human keratinocytes (KCs) exposed to the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). Our data revealed that green light effectively reduces the mRNA expression of pro-inflammatory cytokines IL-6, IL-8, and TNF-α, comparably to the effect of dexamethasone, a conventional anti-inflammatory agent. As Nuclear factor erythroid-2-related factor 2 (Nrf2) is involved in the red light response, we explored Nrf2′s role in green light anti-inflammatory activity. Green light exposure activated the Nrf2 pathway, leading to Nrf2 increased accumulation in KCs and the induction of Nrf2 target genes, including HO-1 and GCLC. Invalidation of Nrf2 with si-RNA diminished the green light's regulatory effect, indicating Nrf2′s essential role in the green light's anti-inflammatory action. As the Transient Receptor Potential Vanilloid 1 (TRPV1) channel is a potential target for green light, we investigated its role in PBM response. Blocking TRPV1 with capsazepine (CPZ) abolished the anti-inflammatory effect of green light and prevented the upregulation of Nrf2 target genes. This finding highlights TRPV1′s integral role in green light beneficial activity via the activation of the Nrf2 pathway. Overall, our study identifies TRPV1 and Nrf2 as critical players in the green light response, highlighting the versatility of PBM in controlling skin inflammation.

Keywords

• Keratinocyte
• Inflammation
• TRPV1
• Nrf2
• Photobiomodulation
• Green light