Capsiate inhibits ultraviolet B-induced skin inflammation by inhibiting Src family kinases and epidermal growth factor receptor signaling.
Capsiate, one of the major capsaicinoids, is nonpungent and present in sweet pepper. We investigated the effects of capsiate on the ultraviolet B (UVB)-induced inflammatory response in skin and its molecular mechanisms. Capsiate-pretreated human keratinocytes inhibited intracellular reactive oxygen species (ROS), which activate the mitogen-activated protein kinase and nuclear factor-kappaB (NF-kappaB) pathways. Therefore, we determined the effects of capsiate on these pathways. Capsiate inhibited UVB-induced cyclooxygenase-2 (COX-2) expression, extracellular signal-related kinase 1/2 phosphorylation, nuclear translocation of NF-kappaB, and the expression of proinflammatory cytokines and potent angiogenic factors, including vascular endothelial cell growth factor and matrix metalloproteinase-2 (MMP-2) and MMP-9. In addition, capsiate inhibited UVB-induced epidermal growth factor receptor (EGFR) activation, which reduces the levels of proinflammatory cytokines and angiogenic factors. We also investigated the photoprotective effects of capsiate in vivo. Topical treatment with capsiate significantly decreased UVB-induced skin damage and inhibited the expression of COX-2, proinflammatory cytokines, and angiogenic factors, including platelet/endothelial cell adhesion molecule-1 and intercellular adhesion molecule-1. Inhibition of Src kinase activity and ROS may inhibit the EGFR activation. Therefore, capsiate may protect the skin from UVB-induced adverse effects and these results provide a molecular basis for understanding its effects on inflammation and angiogenesis.
Lee
Eun-Jung
EJ
Laboratory of Dermatology-Immunology, Catholic Research Institute of Medical Science, Catholic University, Seoul 137-040, South Korea.
Jeon
Myung-Shin
MS
Kim
Byung-Dong
BD
Kim
Jeong-Han
JH
Kwon
Young-Guen
YG
Lee
Hyangkyu
H
Lee
Yun Sang
YS
Yang
Jeong-Hee
JH
Kim
Tae-Yoon
TY
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003872:Dermatitis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000517:prevention & control; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D019061:src-Family Kinases / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D066246:ErbB Receptors; D019061:src-Family Kinases; C470213:capsiate; D002211:Capsaicin