Physiological Doses of Red Light Induce IL‐4 Release in Cocultures between Human Keratinocytes and Immune Cells

Abstract

Phototherapy is routinely used for the treatment of various skin conditions and targeted therapy of superficial cancers. However, the molecular mechanisms behind their biological effects and the need for efficacy enhancing photosensitizers are not well addressed. Particularly, not much is known about the inherent effect of light from the visible spectrum on cytokine release and its downstream effects in keratinocytes and immune cells located in skin and therefore exposed to light. To address this, we delivered calibrated doses of well-defined light qualities (380 to 660 nm) to cocultures of human keratinocytes and macrophage/dendritic cells in the absence or presence of the commonly used photosensitizer 8-methoxypsoralen (8-MOP). The experiments identified IL-4 as a key effector cytokine released by this coculture model with need for 8-MOP in the UVA 1 /blue (380 nm) and no requirement for photosensitizer in the red light spectrum (627 nm). 3D organotypic skin cultures treated with IL-4 showed thickening of the epidermal layer and delayed differentiation. However unlike IL-4 and UVA 1 /blue light treatment, red light did not reduce the expression of keratinocyte differentiation markers or increase signs of photo-oxidative damage. This supports the application of isolated red light as a possible alternative for photo-immunotherapy without need for additional photosensitizers.Abbreviations: UVA 1 , long-wavelength ultraviolet A (380 nm); 8-MOP, 8-methoxypsoralen; PUVA, psoralen plus UVA;PDT, photodynamic therapy; M//DCs, macrophage/dendritic cell cultures; ROS, reactive oxygen species; KRT1, keratin 1; KRT10, keratin 10.

Combination of Natural Extracts and Photobiomodulation in Keratinocytes Subjected to UVA Radiation

“…Despite this absence of difference regarding the CT in terms of living cells, other parameters related to cell signaling and photoaging may present improvements with use of the extract. The modulation in expression of anti‐ and proinflammatory cytokines, metalloproteinases, and DNA repair genes are some of the factors which may be influenced by PBM and fig extract and need further investigation.…”

Effects of visible light on mechanisms of skin photoaging

“…43 Red light (627 nm; 0.5-5 J/ cm 2 ) exposure can induce the anti-inflammatory cytokine, IL-4, in human keratinocytes and macrophage/dendritic cells through mechanisms not mediated by photo-oxidative mechanisms without the need for a photosensitizer, implicating its potential utility in phototherapy. 21…”

“…This may explain why longer wavelengths are not as deleterious in inducing photoaging changes 20 . Blue light has also been found to work through flavins and opsins in cells, while UVA and red light have been found to not work through opsins 12,21 . Instead, low‐intensity red light has been found to act on cells through the photoacceptor cytochrome C oxidase, the terminal enzyme of the mitochondrial electron transport chain 22 …”

“…At a single dose of 5.0 J/cm 2 and two or three doses of 2.5 J/cm 2 increased cell migration and cell proliferation and maintenance of cell viability were observed, whereas exposures at 16 J/cm 2 produced the opposite effect 43 . Red light (627 nm; 0.5‐5 J/cm 2 ) exposure can induce the anti‐inflammatory cytokine, IL‐4, in human keratinocytes and macrophage/dendritic cells through mechanisms not mediated by photo‐oxidative mechanisms without the need for a photosensitizer, implicating its potential utility in phototherapy 21 …”

Untitled

“…Подальше підвищення концентрацій IЛ-4 на стадіях переходу проліферації в стадію ремоделювання і, власне, ремоделювання пов'язано, мабуть, зі здатністю IЛ-4 спільно з IЛ-13, а також IЛ-4R і IЛ-13R активувати транскрипцію перетворювача сигналу й активатора транскрипції 6 (STAT6), що стоїть нижче, та сприяти поляризації макрофагів другого типу, пов'язаних з репаративним фенотипом і протизапальною дією [15]. У літературі показана стійка індукція IЛ-4 в результаті впливу червоного світла в 3D-моделі шкіри [16]. Низькоінтенсивна лазерна терапія приводила також до підвищення експресії IЛ-4 при нейрозапаленні на 3-й, 7-й і 14-й дні після пошкодження [17].…”