Chimyl Alcohol Suppresses PGE2 Synthesis by Human Epidermal Keratinocytes through the Activation of PPAR-γ

Alkyl glyceryl ethers (AKGs) are widely used as emulsion stabilizers, and their anti-inflammatory effects are well known. Daily exposure to environmental stresses, such as chemicals, low humidity and ultraviolet LIGHT (UV), can initiate and promote the development of various skin problems. Among those stresses, it has been established that UV induces skin pigmentation and accelerates premature skin aging due to the inflammation that results. Here, we investigated whether chimyl alcohol (CA), which is an AKG, suppresses the inflammatory process. The suppression of cell damage and the reduction of intracellular levels of Reactive Oxygen Species (ROS) in normal human epidermal keratinocytes (NHEKs) after UVB exposure was evaluated using the Neutral red (NR) and the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) assays, respectively. Moreover, the expression levels of mRNAs and proteins related to inflammation were evaluated by Real-time RT-PCR and ELISA assays, respectively. CA suppressed prostaglandin E₂ (PGE₂) production in UVB-exposed NHEKs according to the down-regulated expression level of cyclooxygenase-2 (COX-2) mRNA. Furthermore, CA up-regulated the mRNA expression levels of Peroxisome Proliferator-activated Receptor (PPAR)-γ, nuclear factor E2-related factor 2 (Nrf2) and γ-glutamyl cysteine synthase (γ-GCS) in NHEKs. Finally, we examined the effects of CA on siPPAR-γ transfected NHEKs. siPPAR-γ transfection of NHEKs abolished the mRNA expression levels of Nrf2 and UVB-stimulated PGE₂ secretion that were regulated by CA. Hence, CA suppresses the UVB-induced COX-2 mRNA expression and PGE₂ production through PPAR-γ as an agonist. We conclude that CA provides useful protection and/or alleviation against UV damage.

Nrf2; PPAR-γ; UVB; chimyl alcohol; γ-GCS.