title: [Naringenin may block RSV-induced mucous hypersecretion in A549 cell via JNK/AP-1 signaling pathway].
abstract: OBJECTIVE
  Naringenin has been reported to attenuate Mucin (MUC) 5AC secretion in many pathological models. Many stimuli activate MUC5AC expression through JNK/AP-1 signaling pathways. We hypothesized that naringenin may have inhibitory effects on mucous hypersecretion by modulating MUC5AC production and inhibiting JNK/AP-1 signaling pathways.
  
  
  METHODS
  The cell model of mucous hypersecretion was made by human lung adenocarcinoma epithelial (A549) cells stimulated by RSV. A549 cells were subcultured and then randomly divided into 7 groups, which were designated as group C (cell control group), groups R1-3 (cells were infected with RSV at the multiplication of infection (MOI) of 0. 5, 1. 0, 5. 0), groups N1-2 (cells infected with viruses in presence of Nar 30 - 100 mol/L), groups N3-4 (uninfected cells treated with Nar 30 - 100 µmol/L), group D (DMSO), group S (cells infected with viruses in presence of SP600125). After incubating for 24 hrs, the expression of MUC5AC at mRNA and protein level in the groups were determined by real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). The protein expression changes of JNK, p-JNK and AP-1 were measured by Western blotting.
  
  
  RESULTS
  The expressions of MUC5AC protein and mRNA in all RSV infected groups were significantly higher than that in group C in a dose-dependent manner (all P <0. 05). Nar of 30 and 100 µmol/L significantly and dose-dependently decreased RSV-induced secretion of MUC5AC protein in cell supernatant and expression of MUC5AC mRNA (P <0. 05). The relative content of p-JNK, AP-l in R2 groups were 3. 31 ± 0. 34 and 1. 94 ± 0. 05. Theyfrweremtgnificanty increased as compared with group C (both 1. 00 ± 0. 00) (all P <0. 05). The levels of p-JNK in N2 and S groups were 2. 10 ± 0. 20. 27 and 1.±97 ± 0. 16. The levels of AP-1 in N2 and S groups were 1. 40 ± 0. 03, 1. 36 ± 0. 05. Nar and SP600125 led to a largest decrease in levels of p-JNK and AP-1 when compared with group R2 (P <0. 05). The MUC5AC protein in group R2 was (48. 19 ± 0. 47) µg/L. The protein expression of MUC5AC in group R2 was significantly higher than that in group C [(36. 67 ± 1. 50) g/L] with a statistically significant difference (P <0. 05). The protein expression of MUC5AC in groups N2 and S were(43. 17 ± 1. 06) µg/L, (44.±02 ± 0. 99) µg/L, Nar and SP600125 remarkably inhibited RSV-induced secretion of MUC5AC in supernatant of A549 cells (P < 0. 05).
  
  
  CONCLUSIONS
  Naringenin might be able to block RSV-induced mucous
authors.forename: Shanshan
authors.initials: S
authors.lastname: Meng
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wu
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Hu
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
authors.forename: Changchong
authors.initials: C
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma; D000077192:Adenocarcinoma of Lung; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms; D055271:Mucin 5AC / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism*; D011897:Random Allocation; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000187:drug effects*
chemical_list: D044950:Flavanones; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D018808:Transcription Factor AP-1; C005273:naringenin