Ultraviolet B radiation (UVB) activates mitogen-activated protein kinases (MAPK): p38, extracellular signal regulated (ERK), and c-Jun N-terminal (JNK) kinases in human skin cells. Human keratinocytes (KC) exposed to UVB secrete several cytokines (CK), among which the growth differentiation factor-15 (GDF-15) is augmented in inflammatory and aging processes and the granulocyte macrophage-colony stimulating factor (GM-CSF) is involved in cell proliferation, differentiation, and survival, and both CK have implications in skin carcinogenesis. We assessed p38, ERK, JNK, GDF-15, and GM-CSF in UVB-exposed skin cells and a red grape (Vitis vinifera) seed extract's (GSE) capacities to regulate these pathways in UVB-exposed KC. Two concentrations of the GSE extract were selected: GSE1 (37.5 μgEqGA/mL) and GSE2 (75 μgEqGA/mL) and a UVB dose (100 mJ/cm2) within the physiological range. Molecules were assessed with ELISA, semiquantitative results being confirmed by Western blot. UVB triggered the signaling molecules' phosphorylation and the concentrations of CK. All molecules but GM-CSF increased early, at 2 h, from UVB exposure while GM-CSF increased later (at 8 h). MAPK and GDF-15 were regulated by GSE1; GM-CSF, by the higher concentration, GSE2. The amplitude and kinetics of the responses were diverse according to time point, molecules, and the extract's concentration. GSE exerted beneficial effects on MAPK and CK triggered by UVB in human skin cells: reduction of phosphorylation of the assessed signaling molecules and anti-inflammatory effects. Targeting MAPK and specific inflammatory mediators such as GDF-15 and GM-CSF with GSE in UVB-induced skin cells represents a novel and a promising starting point for future photoprotection strategies.

中文翻译：

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用葡萄籽提取物靶向UVB激活的人皮肤细胞中的MAPK（p38，ERK，JNK）和炎症性CK（GDF-15，GM-CSF）。

紫外线B辐射（UVB）激活人皮肤细胞中的促分裂原活化蛋白激酶（MAPK）：p38，细胞外信号调节（ERK）和c-Jun N端（JNK）激酶。暴露于UVB的人角质形成细胞（KC）分泌多种细胞因子（CK），其中在炎症和衰老过程中增强了生长分化因子15（GDF-15），并且涉及粒细胞巨噬细胞集落刺激因子（GM-CSF）在细胞增殖，分化和存活方面，CK均与皮肤癌变有关。我们评估了暴露于UVB的皮肤细胞中的p38，ERK，JNK，GDF-15和GM-CSF，以及评估红葡萄（Vitis vinifera）种子提取物（GSE）调节暴露于UVB的KC中这些途径的能力。选择了两种浓度的GSE提取物：GSE1（37。5μgEqGA/ mL）和GSE2（75μgEqGA/ mL）和UVB剂量（100 mJ / cm2）在生理范围内。用ELISA评估分子，通过Western印迹证实半定量结果。UVB触发信号分子的磷酸化和CK的浓度。除GM-CSF外，所有分子均从UVB暴露于2 h早期增加，而GM-CSF较晚（8 h）增加。MAPK和GDF-15受GSE1调控。GM-CSF，浓度更高，GSE2。反应的幅度和动力学根据时间点，分子和提取物的浓度而变化。GSE对人皮肤细胞中UVB触发的MAPK和CK产生了有益的作用：减少了评估的信号分子的磷酸化和抗炎作用。