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.
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.
Kang
Jae Seung
JS
Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Kim
Ha Na
HN
Jung
Da Jung
DJ
Kim
Jee Eun
JE
Mun
Ga Hee
GH
Kim
Yeong Seok
YS
Cho
Daeho
D
Shin
Dong Hoon
DH
Hwang
Young-Il
YI
Lee
Wang Jae
WJ
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D029363:Organic Anion Transporters, Sodium-Dependent / Q000096:biosynthesis*; D021381:Protein Transport; D017382:Reactive Oxygen Species; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000096:biosynthesis*; D014466:Ultraviolet Rays
D000975:Antioxidants; C515334:CCR2 protein, human; D016209:Interleukin-8; D029363:Organic Anion Transporters, Sodium-Dependent; D017382:Reactive Oxygen Species; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D001205:Ascorbic Acid