Phosphodiesterase 4B plays a role in benzophenone-3-induced phototoxicity in normal human keratinocytes
Hyoung-June Kim1, Eunyoung Lee2, Moonyoung Lee2
1Basic Research and Innovation Division, AmorePacific Corporation R&D Center, Yongin, Gyeounggi-do 17074, Republic of Korea.
Abstract:
Benzophenone-3 (BP-3), which is extensively used in organic sunscreen, has phototoxic potential in human skin. Phosphodiesterase 4B (PDE4B) has a well-established role in inflammatory responses in immune cells. Currently, it is unknown if PDE4B is associated with BP-3-induced phototoxicity in normal human keratinocytes (NHKs). We found that BP-3 significantly increased PDE4B expression in ultraviolet B (UVB)-irradiated NHKs. Notably, BP-8, a sunscreen agent that shares the 2-hydroxy-4-methoxyphenyl methanone moiety with BP-3, also upregulated PDE4B expression in NHKs. Upon UVB irradiation, BP-3 upregulated the expression of pro-inflammatory factors, such as prostaglandin endoperoxide synthase 2, tumor necrosis factor α, interleukin 8, and S100A7, and downregulated the level of cornified envelope associated proteins, which are important in the development of the epidermal permeability barrier. The additive effects of UVB-activated BP-3 on the expression of both pro-inflammatory mediators and cornified envelope associated proteins were antagonized by treatment with the PDE4 inhibitor rolipram. The BP-3 and UVB co-stimulation-induced PDE4B upregulation and its association with the upregulation of pro-inflammatory mediators and the downregulation of epidermal differentiation markers were confirmed in a reconstituted three dimensional human epidermis model. Therefore, PDE4B has a role in the mechanism of BP-3-induced phototoxicity.
Insights
Benzophenone-3 (BP-3) sunscreen can cause skin phototoxicity by increasing PDE4B. This enzyme is linked to inflammation and barrier dysfunction, but can be inhibited by rolipram, suggesting a therapeutic target.
Area of Science:
- Dermatology
- Photobiology
- Immunology
Background:
- Benzophenone-3 (BP-3) is a common organic sunscreen ingredient with known phototoxic potential.
- Phosphodiesterase 4B (PDE4B) plays a key role in immune cell inflammatory responses.
- The link between BP-3 phototoxicity and PDE4B in human keratinocytes is not well understood.
Purpose of the Study:
- To investigate the role of Phosphodiesterase 4B (PDE4B) in Benzophenone-3 (BP-3)-induced phototoxicity in normal human keratinocytes (NHKs).
- To explore the effects of BP-3 and ultraviolet B (UVB) irradiation on PDE4B expression and downstream inflammatory pathways.
- To assess the potential of PDE4 inhibition as a countermeasure against BP-3 phototoxicity.
Main Methods:
- Normal human keratinocytes (NHKs) and a 3D human epidermis model were exposed to ultraviolet B (UVB) and Benzophenone-3 (BP-3).
- Expression levels of PDE4B, pro-inflammatory factors (prostaglandin endoperoxide synthase 2, tumor necrosis factor α, interleukin 8, S100A7), and epidermal differentiation markers were analyzed.
- The effect of the PDE4 inhibitor rolipram on BP-3 and UVB-induced changes was evaluated.
Main Results:
- BP-3 significantly increased PDE4B expression in UVB-irradiated NHKs.
- BP-3 and UVB co-exposure upregulated pro-inflammatory mediators and downregulated epidermal barrier proteins.
- The PDE4 inhibitor rolipram antagonized the effects of BP-3 and UVB on inflammatory and barrier proteins.
Conclusions:
- Phosphodiesterase 4B (PDE4B) is involved in the mechanism of Benzophenone-3 (BP-3)-induced phototoxicity.
- BP-3 and UVB irradiation promote inflammation and impair skin barrier function via PDE4B.
- Targeting PDE4B may offer a strategy to mitigate BP-3-induced skin damage.
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