Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α-induced HaCaT human keratinocytes.
Previous studies found that phloretin had anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, we investigated whether phloretin could suppress the production of the intercellular adhesion molecule (ICAM)-1 and chemokines through downregulation of the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-stimulated HaCaT human keratinocytes. HaCaT cells were treated with phloretin and then the cells were stimulated by TNF-α. Phloretin treatment decreased the production of IL-6, IL-8, CCL5, MDC, and TARC. Phloretin decreased ICAM-1 protein and mRNA expression, and also suppressed the adhesion of monocyte THP-1 cells to inflammatory HaCaT cells. Phloretin inhibited NF-κB translocation into the nucleus and also suppressed the phosphorylation of Akt and MAPK signal. In addition, phloretin increased heme oxygenase-1 production in a concentration-dependent manner. These results demonstrated that phloretin has anti-inflammatory effects to inhibit chemokines and ICAM-1 expressions through suppression of the NF-κB and MAPK pathways in human keratinocytes.
Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan.
Wen-Chung
WC
Huang
Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan; Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, 261 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan.
Yi-Wen
YW
Dai
Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, 261 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan.
Hui-Ling
HL
Peng
Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, 261 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan.
Chiao-Wei
CW
Kang
Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, 261 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan.
Chun-Yu
CY
Kuo
Department of Nursing, Chang Gung University of Science and Technology, 261 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan. Electronic address: ccliu@gw.cgust.edu.tw.
Chian-Jiun
CJ
Liou
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D010693:Phloretin
Chemokines; ICAM-1; MAPK; NF-κB; Phloretin