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Helicobacter pylori Induces Increased Expression of Toll‐Like Receptors and Decreased Toll‐Interacting Protein in Gastric Mucosa that Persists Throughout Gastric Carcinogenesis

2012; Wiley; Volume: 18; Issue: 1 Linguagem: Inglês

10.1111/hel.12008

1523-5378

Pedro Pimentel‐Nunes, Nádia Gonçalves, Inês Boal‐Carvalho, Luís Pedro Afonso, Paula Lopes, Roberto Roncon‐Albuquerque, Rui Henrique, Luís Moreira‐Dias, Adelino Leite‐Moreira, Mário Dinis‐Ribeiro,

Immune Response and Inflammation

Abstract Background Toll‐like receptors ( TLR ) are essential for H elicobacter pylori ( HP ) recognition. Their role in the progression of gastric lesions leading to cancer is not established. Aim To evaluate for the first time in humans the expression of TLR 2, TLR 4, and TLR 5, as well as the expression of other related molecules in the entire sequence of gastric lesions. Methods Biopsy samples (n = 80, 48% HP +) from normal mucosa, HP gastritis, metaplasia, dysplasia or adenocarcinoma were obtained from 44 patients. m RNA quantification of TLR 2, TLR 4, TLR 5, T oll‐interacting protein ( TOLLIP ), PPAR ‐γ, NF ‐κ B , TNF ‐α, COX ‐1, COX ‐2, and CDX ‐2 was performed by real‐time RT‐PCR . TLR 2, TLR 4, and TLR 5 protein expression was quantified by immunohistochemistry. Results When compared to normal mucosa (1.0 arbitrary unit ( AU )), HP gastritis presented higher expression of TLR 2 (2.23 ± 0.36 AU ), TLR 4 (1.92 ± 0.40 AU ) and TNF ‐α (2.14 ± 0.50 AU ) and lower TOLLIP and PPAR γ expression (0.72 ± 0.12 AU , p < .05 all genes). Metaplasia and dysplasia/carcinoma presented higher expression of TLR 2 (1.66 ± 0.46 and 1.48 ± 0.20 AU , respectively, p < .05), lower expression of TOLLIP (0.66 ± 0.09 and 0.52 ± 0.04 AU , p < .05) and PPAR γ (0.73 ± 0.12 and 0.63 ± 0.10 AU , p < .05). The significant trend for decrease in TOLLIP and PPAR γ was associated with increasing levels of CDX ‐2 from normal mucosa to carcinoma ( p < .05), translating that in diffuse and higher TLR s protein expression ( p < .05). Conclusion Gastric carcinogenesis is associated with decreasing levels of TLR s inhibitors and elevated TLR s levels throughout all the spectrum of lesions. Future studies should investigate if modulation of these receptors activity may influence gastric carcinogenesis and tumor progression.