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

• Published in: Helicobacter (Cambridge, Mass.) Mass.), 2013-02, Vol.18 (1), p.22-32
• Main Authors: Pimentel-Nunes, Pedro, Gonçalves, Nádia, Boal-Carvalho, Inês, Afonso, Luís, Lopes, Paula, Roncon-Albuquerque Jr, Roberto, Henrique, Rui, Moreira-Dias, Luís, Leite-Moreira, Adelino F., Dinis-Ribeiro, Mário
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy; Carcinogenesis; Carcinoma; Cross-Sectional Studies; Cyclooxygenase-1; Cyclooxygenase-2; Dysplasia; Female; Gastric cancer; Gastric mucosa; Gastric Mucosa - immunology; Gastric Mucosa - microbiology; Gastric Mucosa - pathology; Gastritis; Gene Expression Profiling; Helicobacter Infections - complications; Helicobacter Infections - immunology; Helicobacter Infections - microbiology; Helicobacter Infections - pathology; Helicobacter pylori; Helicobacter pylori - immunology; Helicobacter pylori - pathogenicity; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins - biosynthesis; Intracellular Signaling Peptides and Proteins - immunology; Male; Metaplasia; Middle Aged; mRNA; NF- Kappa B protein; Peroxisome proliferator-activated receptors; Polymerase chain reaction; PPARγ; Real-Time Polymerase Chain Reaction; Stomach Neoplasms - immunology; Stomach Neoplasms - microbiology; Stomach Neoplasms - pathology; TLR2; TLR2 protein; TLR4; TLR4 protein; TLR5 protein; Toll-interacting protein; Toll-like receptors; Toll-Like Receptors - biosynthesis; Toll-Like Receptors - immunology; Tumor necrosis factor- alpha; Tumors
• ISSN: 1083-4389; 1523-5378
• DOI: 10.1111/hel.12008

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. mRNA quantification of TLR2, TLR4, TLR5, Toll‐interacting protein (TOLLIP), PPAR‐γ, NF‐κB, 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