Anti-inflammatory effect of capsaicin in Helicobacter pylori-infected gastric epithelial cells.
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.
Lee
In Ohk
IO
The Brain Korea 21 Project for Medical Science, Seoul, Korea.
Lee
Kwang Hyoung
KH
Pyo
Jae Hee
JH
Kim
Jie Hyun
JH
Choi
Yeun Jung
YJ
Lee
Yong Chan
YC
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016209:Interleukin-8; D016328:NF-kappa B; D002211:Capsaicin