Decreased Toll-interacting protein and peroxisome proliferator-activated receptor gamma are associated with increased expression of Toll-like receptors in colon carcinogenesis

• Type: Article in International Scientific Journal
• Date: 2012

Authors

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

Journal

Title: JOURNAL OF CLINICAL PATHOLOGY

Vol. 65

Pages: 302-308

ISSN: 0021-9746

Indexing

ISI Web of Knowledge - 28 Citations

Scopus - 34 Citations

Other information

Authenticus ID: P-002-BR9

DOI: 10.1136/jclinpath-2011-200567

Abstract (EN): Background Animal data suggest that Toll-like receptors (TLR) may play an important role in colon carcinogenesis. Studies in humans to support that hypothesis are scarce. Aim To evaluate the expression of TLR2, TLR4 and TLR5, and the expression of several other related molecules, in different human colonic lesions. Methods Colon biopsy samples from normal mucosa, normal mucosa adjacent to lesion, adenoma or sporadic carcinoma were obtained from 35 consecutive patients undergoing colonoscopy. Quantification of TLR2, TLR4, TLR5, Toll-interacting protein (TOLLIP), peroxisome proliferator-activated receptor gamma (PPAR-gamma), nuclear factor kappa B, tumour necrosis factor (TNF) alpha, cyclooxygenase (COX) 1 and 2 mRNA was performed by real-time reverse transcription PCR. TLR2, TLR4 and TLR5 protein expression was quantified by immunohistochemistry. Results When compared with normal mucosa (1.0 arbitrary unit (AU)), adjacent normal mucosa presented higher expression of COX-2 (1.86 +/- 0.3 AU, p=0.01) and TNF alpha (1.44 +/- 0.18 AU, p=0.04) and lower TOLLIP expression (0.75 +/- 0.05 AU, p=0.004). Adenomas and carcinomas presented higher expression of COX-2 (1.63 +/- 0.27 and 1.38 +/- 0.14 AU, p=0.03 and p=0.05, respectively) and lower expression of TOLLIP (0.44 +/- 0.04 AU, p<0.001), with diffuse and higher TLR protein expression (p<0.001). Carcinomas also expressed higher TLR2 (2.31 +/- 0.32 AU, p=0.006) and lower PPAR-gamma (0.56 +/- 0.12 AU, p=0.003). There was a trend towards decreased TOLLIP (p<0.001) and PPAR-gamma (p=0.05) from normal mucosa to adenoma/carcinoma. Conclusions Persistently positive TLR expression and lower expression of TLR inhibitors was associated with higher TLR protein levels throughout the spectrum of lesions of colon carcinogenesis. Increasing activation of these receptors by bacteria may play a crucial role in colon carcinogenesis and tumour progression.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7