The Korean Journal of Gastroenterology (대한소화기학회지)

The Korean Society of Gastroenterology (대한소화기학회)
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Increased Expression of Toll-Like Receptor-4 in Helicobacter pylori Infected Gastric Mucosa

Helicobacter pylori 감염증에서 위점막의 Toll-like Receptor 4 발현

Park, Joon-Yong;Han, Dong-Soo;Kim, Bo-Hyun;Kang, Eun-Kyung;Li, Ying-Chun;Lee, Hang-Lak;Kim, Jin-Bae;Shon, Joo-Hyun;Choi, Ho-Soon;Kang, Jung-Ock;Hahm, Joon-Soo
박준용;한동수;김보현;강은경;이영춘;이항락;김진배;손주현;최호순;강정옥;함준수

  • Published : 20030300
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Abstract

Background/Aims: Toll-like receptors (TLRs) represent a pattern recognition receptors with an ability of specific recognition of pathogens. TLRs appear to respond to pathogens and induce NF-$\kappa$B activation. TLR2 and 4 seem to be related to the initiation of immune response against gram negative and positive bacteria. We investigated the effect of Helicobacter pylori (H. pylori) infection on the expression of TLRs on the gastric mucosa. Methods: For 35 endoscopic gastric mucosa samples, histologic grading of H. pylori infection and inflammatory cell infiltration were performed. The mRNA expression of TLR2, 3, and 4 was examined by RT-PCR. Immunohistochentistry demonstrated the distribution of TLR2 and 4 in gastric mucosal biopsies. Results: H. pylori positive gastric mucosa expressed higher TLR4/GAPDH ratio than H. pylori negative gastric mucosa (p=0.035), while no significant difference in the expression of TLR2 and 3 was detected (p=0.129, p=0.176). The severity of neutrophil infiltration showed a significant positive correlation with TLR4/GAPDH ratio (p=0.045, r=0.342). Immunohistochentistry using anti-TLR4 and anti-TLR2 antibody revealed the expression of TLR4 in the epithelial cells of H. pylori-infected gastric mucosa. Conclusions: H. pylori infection induces TLR4 expression in the human gastric epithelium, which suggests a certain role of TLR4 in the mucosal inflammatory reaction to H. pylori infection.

목적: Toll-like receptor (TLR)는 특이한 형태의 몇 가지 항원을 인지하는 형태 인지 수용체로서 항원에 반응하여 NF-$\kappa$B의 활성을 유도하는 일련의 과정을 기시하는 데 관여하는 것으로 알려져 있다. 그 중 TLR-2와 TLR-4는 그람 양성과 음성군에 의해 유발되는 염증반응에 관여한다. 본 연구에서 H. pylori가 위점막에서 TLR의 과발현에 미치는 영향에 대해 확인하였다. 대상 및 방법: 상부위장관 내시경 검사를 시행한 35명에서 위점막 검체를 얻었다. H. pylori 감염 여부의 확인을 위한 rapid urease test와 조직학적 검사를 시행하여 H. pylori 감염 정도와 염증세포들의 침윤 정도를 확인하였다. 역전사 PCR을 통해 TLR-2, 3, 4의 전령 RNA의 발현 정도를 확인하였고, 변역조직화학검사를 통해 위점막 검체에서 TLR의 발현 위치를 밝혔다. 결과 35명의 환자에서 얻어진 위점막 검체 중 H. pylori 감염을 확인 한 16개의 검체에서 TLR-4/GAPDH 비가 유의하게 높았다 (p=0.035) 그러나 TLR-2, 3에서는 유의한 차이는 관찰할 수 없었다. 항TLR-4항체와 항TLR-2 항체를 이용한 면역조직화학검사에서 점막의 상피세포에 TLR-4의 발현증가가 있었다. 결론: H. pylori 감염이 위점막에서 TLR-4의 발현을 증가시킴을 확인하였고, TLR-4의 활성이 H. pylori에 의해 유발되는 일련의 면역반응에 중요한 역할을 하는 것으로 생각한다.

Keywords

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