title: Inhibition of TNF-α/IFN-γ induced RANTES expression in HaCaT cell by naringin.
abstract: BACKGROUND
  Naringin is a bioflavonoid derivative and is predominantly found in Citrus paradisi Macf., Citrus sinensis (Linn.) Osbeck, Citrus unshiu Marc., Citrus reticulata Blanco cv. Nobilis, Citrus tachibana (Makino) Tanaka, Citrus junos Sieb. ex Tanaka (Rutaceae), and related citrus species. It has anti-inflammatory effects that have been well-documented, but the mechanism is poorly characterized.
  
  
  OBJECTIVE
  The effect of naringin on production of RANTES (regulated upon activation normal T-cell expressed and secreted) in human HaCaT cells was investigated here for the first time.
  
  
  METHODS
  The HaCaT cells were cultured in Dulbecco's modified Eagle's medium (DMEM) and the proliferation of cell was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The cells were divided into three groups including control group, tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ)-stimulated group, and naringin pretreatment group (first incubated in the presence of naringin and then exposed to TNF-α/IFN-γ). The concentration of RANTES in the supernatants was determined by enzyme-linked immunosorbent assay (ELISA). The expression of RANTES mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) P65 protein was detected with immunocytochemical method and western blot method.
  
  
  RESULTS
  Naringin hardly inhibits HaCaT cells growth at concentrations rising from 0.25 to 1 mmol/L. However, RANTES expression detected in supernatant stimulated with TNF-α/IFN-γ reduced 15 and 16%, respectively, when cultured with 0.25, 0.5 mmol/L naringin. Furthermore, 1 mmol/L naringin significantly decreased RANTES mRNA level. Finally, naringin decreased the expression of NF-κB P65 protein in nuclei.
  
  
  CONCLUSIONS
  Naringin can inhibit the increased production of RANTES, which is partially via NF-κB-dependent signal pathway.
authors.affiliation: Department of Pharmacology, West-China Medical Center, Sichuan University, Chengdu, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Si-Si
authors.forename: Liu
authors.initials: L
authors.lastname: Liao
authors.forename: Zhu
authors.initials: Z
authors.lastname: Ling
authors.forename: Yang
authors.initials: Y
authors.lastname: Yun-Xia
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D002957:Citrus; D004847:Epithelial Cells; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D015603:Keratinocytes; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018946:Chemokine CCL5; D044950:Flavanones; D016328:NF-kappa B; D028321:Plant Preparations; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C022616:thiazolyl blue; C005274:naringin