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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Pedro Pimentel-Nunes (Author) FMUP; Goncalves, N (Author) FMUP; Boal Carvalho, I (Author) Other; Afonso, L (Author) Other; Lopes, P (Author) Other; Roncon-Albuquerque R Jr (Author) FMUP; henrique, rmf (Author) ICBAS; Moreira Dias, L (Author) Other; Leite-Moreira AF (Author) FMUP; Mario Dinis Ribeiro (Author) FMUP

Journal

Title: Helicobacter

Vol. 18

Pages: 22-32

ISSN: 1083-4389

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 47 Citations

Scopus - 56 Citations

Other information

Authenticus ID: P-002-121

DOI: 10.1111/hel.12008

Abstract (EN): 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 similar to=similar to 80, 48% HP+) from normal mucosa, HP gastritis, metaplasia, dysplasia or adenocarcinoma were obtained from 44 patients. mRNA quantification of TLR2, TLR4, TLR5, Toll-interacting protein (TOLLIP), PPAR-?, NF-?B, TNF-a, 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 similar to +/-similar to 0.36 AU), TLR4 (1.92 similar to +/-similar to 0.40 AU) and TNF-a (2.14 similar to +/-similar to 0.50 AU) and lower TOLLIP and PPAR? expression (0.72 similar to +/-similar to 0.12 AU, p similar to<similar to.05 all genes). Metaplasia and dysplasia/carcinoma presented higher expression of TLR2 (1.66 similar to +/-similar to 0.46 and 1.48 similar to +/-similar to 0.20 AU, respectively, p similar to<similar to.05), lower expression of TOLLIP (0.66 similar to +/-similar to 0.09 and 0.52 similar to +/-similar to 0.04 AU, p similar to<similar to.05) and PPAR? (0.73 similar to +/-similar to 0.12 and 0.63 similar to +/-similar to 0.10 AU, p similar to<similar to.05). The significant trend for decrease in TOLLIP and PPAR? was associated with increasing levels of CDX-2 from normal mucosa to carcinoma (p similar to<similar to.05), translating that in diffuse and higher TLRs protein expression (p similar to<similar to.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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11