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- Title
Helicobacter pylori Induces Increased Expression of Toll-Like Receptors and Decreased Toll-Interacting Protein in Gastric Mucosa that Persists Throughout Gastric Carcinogenesis.
- Authors
Pimentel‐Nunes, Pedro; Gonçalves, Nádia; Boal‐Carvalho, Inês; Afonso, Luís; Lopes, Paula; Roncon‐Albuquerque, Roberto; Henrique, Rui; Moreira‐Dias, Luís; Leite‐Moreira, Adelino F.; Dinis‐Ribeiro, Mário
- Abstract
Background Toll-like receptors ( TLR) are essential for Helicobacter 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 TLR2, TLR4, and TLR5, 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 TLR2, TLR4, TLR5, Toll-interacting protein ( TOLLIP), PPAR-γ, NF-κ B, TNF-α, COX-1, COX-2, and CDX-2 was performed by real-time RT-PCR. TLR2, TLR4, and TLR5 protein expression was quantified by immunohistochemistry. Results When compared to normal mucosa (1.0 arbitrary unit ( AU)), HP gastritis presented higher expression of TLR2 (2.23 ± 0.36 AU), TLR4 (1.92 ± 0.40 AU) and TNF-α (2.14 ± 0.50 AU) and lower TOLLIP and PPARγ expression (0.72 ± 0.12 AU, p < .05 all genes). Metaplasia and dysplasia/carcinoma presented higher expression of TLR2 (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 PPARγ (0.73 ± 0.12 and 0.63 ± 0.10 AU, p < .05). The significant trend for decrease in TOLLIP and PPARγ was associated with increasing levels of CDX-2 from normal mucosa to carcinoma ( p < .05), translating that in diffuse and higher TLRs protein expression ( p < .05). Conclusion Gastric carcinogenesis is associated with decreasing levels of TLRs inhibitors and elevated TLRs levels throughout all the spectrum of lesions. Future studies should investigate if modulation of these receptors activity may influence gastric carcinogenesis and tumor progression.
- Subjects
GASTRIC mucosa; HELICOBACTER pylori; TOLL-like receptors; BIOPSY; DIAGNOSTIC immunohistochemistry; CANCER
- Publication
Helicobacter, 2013, Vol 18, Issue 1, p22
- ISSN
1083-4389
- Publication type
Article
- DOI
10.1111/hel.12008