Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer: Clinico-pathogenic aspects

István Furi, Ferenc Sipos, Tiana M. Germann, Alexandra Kalmár, Zsolt Tulassay, Béla Molnár, Györgyi Muzes

Research output: Contribution to journalReview article

26 Citations (Scopus)

Abstract

Toll-like receptors (TLRs) recognize specific motifs which are frequently present in bacteria, fungi, prokaryotes and viruses. Amongst TLRs, TLR9 can be activated by such bacterial or viral DNA fragments, immunoglobulin-DNA complexes or synthetic oligonucleotides, which all contain unmethylated cytosineguanine nucleotide sequences (CpGs). Emerging data indicate that TLR9 signaling has a role in, and may influence, colorectal carcinogenesis and colonic inflammation. CpGs are classified into three groups according to their influence on both the antigen-specific humoraland cellular immunity, and the production of type 1 interferons and proinflammatory cytokines. TLR9 activation via CpGs may serve as a new therapeutic target for several cancerous and various inflammatory conditions. Due to its probable anti-cancer effects, the application possibilities of TLR9-signaling modulation may be extremely diverse even in colorectal tumors. In this review we aimed to summarize the current knowledge about TLR-signaling in the pathogenesis and therapy of inflammatory bowel diseases and colorectal cancer. Due to the species-specific differences in TLR9 expression, however, one must be careful in translating the animal model data into the human system, because of the differences between CpG-oligodeoxynucleotide-responsive cells. TLR9 agonist DNA-based immunomodulatory sequences could also represent a promising therapeutic alternative in systemic inflammatory conditions and chronic colonic inflammations as their side effects are not significant.

Original languageEnglish
Pages (from-to)4119-4126
Number of pages8
JournalWorld journal of gastroenterology
Volume19
Issue number26
DOIs
Publication statusPublished - Jul 1 2013

Keywords

  • Colorectal cancer
  • DNA-based immunomodulatory sequences
  • Inflammatory bowel diseases
  • Synthetic oligodeoxynucleotide sequences
  • Toll-like receptor 9

ASJC Scopus subject areas

  • Gastroenterology

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