Regulation of UVB-Induced IL-8 and MCP-1 Production in Skin Keratinocytes by Increasing Vitamin C Uptake via the Redistribution of SVCT-1 from the Cytosol to the Membrane

Abstract

It is well known that UVB (290-320 nm) induces inflammation in skin by the transcription and release of cytokines and chemokines from skin keratinocytes. In addition, it is considered that intracellular reactive oxygen species (ROS) plays an important role in UVB-induced inflammatory response in the skin. Therefore, we investigated the effect of vitamin C, a potent antioxidant, on the regulation of UVB-induced skin inflammation via the modulation of chemokines production. Vitamin C uptake into keratinocytes is increased by UVB irradiation in a time- and dose-dependent manner through the translocation of sodium-dependent vitamin C transporter-1 (SVCT-1), a vitamin C-specific transporter, from the cytosol to the membrane. To evaluate the effect of vitamin C on the chemokine mRNA expression, we performed RNase protection assay. As a result, there was a remarkable change in chemokine mRNA expression, especially IL-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, increased IL-8 and MCP-1 mRNA expressions were suppressed by vitamin C treatment. We also confirmed the results of protein levels measured by ELISA. Taken together, vitamin C uptake is increased in UVB-irradiated keratinocytes through the translocation of SVCT-1 and regulates inflammatory response in the skin via the downregulation of IL-8 and MCP-1 production.

An environmental contaminant, benzo(a)pyrene, induces oxidative stress-mediated interleukin-8 production in human keratinocytes via the aryl hydrocarbon receptor signaling pathway

“…Similar BaP-induced IL-8 production via AhR signaling pathway was recently reported in human monocyte-derived macrophages [34]. Since previous studies have already reported that intracellular ROS levels are closely related to IL-8 production in human keratinocytes [9,17], we examined whether or not up-regulation of IL-8 production by NHEKs was inhibited by treatment with NAC, one of ROS inhibitors, and confirmed that ROS is involved in BaP-induced IL-8 production. NAC has been shown to inhibit ROS production directly by scavenging ROS and also indirectly by supplying cysteine for the synthesis of the endogenous antioxidant GSH [35,36].…”

“…6a). Since intracellular ROS levels are shown to be closely related to IL-8 production [9,17], we examined whether or not one of ROS inhibitors, NAC or catalase downregulates the BaP-induced IL-8 production. NHEKs were pretreated with NAC (15 mM) or catalase (500 units/ml) for 2 h before exposure to BaP and were exposed to BaP (1 mM) for 24 h. NAC or catalase inhibited BaP-induced ROS production successfully (Fig.…”

“…Since ROS play an important role in modulating cyto/chemokine production [8,9,17], we next measured the secretion of proinflammatory cyto/chemokines such as IL-1a, IL-6, IL-8, TNF-a and GM-CSF in culture supernatants of NHEKs by ELISA. In the presence of BaP (1 mM) for 24 h, IL-8 production was significantly augmented, whereas the production of IL-1a, IL-6, TNF-a and GM-CSF was not affected (Fig.…”

“…To investigate the proinflammatory effects of BaP on NHEKs, we focused on ROS production because it occurs via the metabolizing process of BaP by CYP1A1 [4,28] and there is compelling evidence that ROS drives the production of oxidative products, which can denature proteins and influence the release of proinflammatory cyto/chemokines, which may be critical for the induction of some inflammatory skin diseases [8,9,17,29]. Furthermore, it is also recognized that ROS can act as a second messenger in the initiation of signal transduction, such as the activation of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) or AP-1 (activator protein 1) and the production of proinflammatory cyto/ chemokines [30].…”

Antioxidants and Skin Aging

“…UV radiation stimulates the translocation of SVCT (sodium-dependent vitamin C transporter-1) in keratinocytes from the cytosol to the cell surface to increase the incorporation of ascorbic acid (Kang et al 2007). That translocation results in the protection of cells against UV-induced oxidative stress.…”