title: Anti-inflammatory effect of capsaicin in Helicobacter pylori-infected gastric epithelial cells.
abstract: OBJECTIVE
  Capsaicin, the main pungent ingredient of hot red and chilli pepper, has been considered as not only a cytoprotective but also a detrimental agent to the gastric mucosa. However, the effect and mechanism of capsaicin that modulate the induction of pro-inflammatory cytokine in Helicobacter pylori-infected epithelial cells have not been investigated previously. Herein, we demonstrated that capsaicin inhibited the release of pro-inflammatory cytokine, interleukin-8 (IL-8) by H. pylori-infected gastric epithelial cells through nuclear factor-kappaB (NF-kappaB) signal pathway.
  
  
  METHODS
  AGS or MKN45 cells as gastric epithelial cells and Vac A+, CagA+ wild-type H. pylori strain ATCC 49503 were used. Gastric epithelial cells were pre-treated with various concentrations of capsaicin and infected with H. pylori for different periods of time to determine IL-8 concentrations in culture supernatant by an ELISA assay. We measured IL-8 mRNA transcripts in H. pylori-infected gastric epithelial cells co-treated with capsaicin by reverse transcriptase-polymerase chain reaction analysis. We performed electrophoretic mobility shift assay to examine the NF-kappaB DNA binding activity with capsaicin and immunofluorescence microscopy to examine nuclear staining of p65. We also performed immunoblotting for IkappaB, IKK activity with capsaicin.
  
  
  RESULTS
  Capsaicin inhibits H. pylori-induced IL-8 production by gastric epithelial cells in dose- and time-dependent manner. Capsaicin as low as 100 micromol/L significantly inhibited IL-8 production in H. pylori-infected MKN45 cells (43.2% of control) at 24 hours incubation, whereas inhibited IL-8 production in H. pylori-infected AGS cells (70% of control). We confirmed that capsaicin inhibited IL-8 mRNA expression after infection of gastric epithelial cells with H. pylori for 6 hours. The addition of capsaicin (100 micromol/L) suppressed H. pylori-induced NF-kappaB activation in gastric epithelial cells at 1 hour post-infection. We also found that the degradation of IkappaB and IKK activation were inhibited by capsaicin.
  
  
  CONCLUSIONS
  Nontoxic dose of capsaicin inhibited H. pylori-induced IL-8 production by gastric epithelial cells through the modulation of IkappaB-, NF-kappaB-, and IL-8 pathways. We conclude that capsaicin can be proposed as a potential anti-inflammatory drug by inhibition of the production of IL-8 in H. pylori-infected gastric epithelium.
authors.affiliation: The Brain Korea 21 Project for Medical Science, Seoul, Korea.
authors.forename: In Ohk
authors.initials: IO
authors.lastname: Lee
authors.forename: Kwang Hyoung
authors.initials: KH
authors.lastname: Lee
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Pyo
authors.forename: Jie Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Yeun Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000472:pathogenicity*; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016209:Interleukin-8; D016328:NF-kappa B; D002211:Capsaicin