Anti-inflammatory effect of capsaicin in Helicobacter pylori-infected gastric epithelial cells

Background and aim: 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-κB (NF-κB) signal pathway. Materials and 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-κB DNA binding activity with capsaicin and immunofluorescence microscopy to examine nuclear staining of p65. We also performed immunoblotting for IκB, 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 μmol/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 μmol/L) suppressed H. pylori-induced NF-κB activation in gastric epithelial cells at 1 hour post-infection. We also found that the degradation of IκB 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 IκB-, NF-κB-, 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.