Abstract
Solar ultraviolet (SUV) irradiation causes skin disorders such as inflammation, photoaging, and carcinogenesis. Cyclooxygenase-2 (COX-2) plays a key role in SUV-induced skin inflammation, and targeting COX-2 may be a strategy to prevent skin disorders. In this study, we found that the expression of COX-2, phosphorylation of p38 or JNKs were increased in human solar dermatitis tissues and SUV-irradiated human skin keratinocyte HaCaT cells and mouse epidermal JB6 Cl41 cells. Knocking down COX-2 inhibited the production of prostaglandin E2 (PGE2), the phosphorylation of p38 or JNKs in SUV-irradiated cells, which indicated that COX-2 is not only the key enzyme for PGs synthesis, but also an upstream regulator of p38 or JNKs after SUV irradiation. The virtual ligand screening assay was used to search for natural drugs in the Chinese Medicine Database, and indicated that salidroside might be a COX-2 inhibitor. Molecule modeling indicated that salidroside can directly bind with COX-2, which was proved by in vitro pull-down binding assay. Ex vivo studies showed that salidroside has no toxicity to cells, and inhibits the production of PGE2, phosphorylation of p38 or JNKs, and secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) caused by SUV irradiation. In vivo studies demonstrated that salidroside attenuates the skin inflammation induced by SUV. In brief, our data provided the evidences for the protective role of salidroside against SUV-induced inflammation by targeting COX-2, and salidroside might be a promising drug for the treatment of SUV-induced skin inflammation.
Highlights
Excessive exposure to solar UV (SUV) is associated with numerous human skin disorders, such as skin inflammation, photoaging, and carcinogenesis [1,2,3]
Previous studies have reported that cyclooxygenase 2 (COX-2) is closely associated with the SUV induced skin inflammation[8], p38 activation is the dominant SUV-induced signaling transduction pathway, and JNKs were activated by both UVA and UVB[5, 6]
The skin inflammation caused by SUV always accompanied with elevated COX-2 and activation of cell signal pathways, such as p38, JNKs [17]
Summary
Excessive exposure to solar UV (SUV) is associated with numerous human skin disorders, such as skin inflammation, photoaging, and carcinogenesis [1,2,3]. SUV comprises approximately 95% UVA and 5% UVB. Exposure to UV is known to induce clustering of some kinds of cell-surface receptors and to transducer intracellular signals [4]. UVA activates p38 and JNKs, while p38 is the primary signaling pathway activated by UVB [5, 6]. These kinases activate their downstream transcription factors, such as nuclear factorkappa B (NF-κB) and (AP-1). The skin inflammation precedes photoaging and carcinogenesis. Anti-inflammation is an important strategy in SUV induced skin disorders
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