title: Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer: clinico-pathogenic aspects.
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 cytosine-guanine 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 humoral- and 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.
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Fűri
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sipos
authors.forename: Tiana M
authors.initials: TM
authors.lastname: Germann
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kalmár
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Béla
authors.initials: B
authors.lastname: Molnár
authors.forename: Györgyi
authors.initials: G
authors.lastname: Műzes
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003092:Colitis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018899:CpG Islands; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009841:Oligonucleotides / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D009841:Oligonucleotides; D051217:Toll-Like Receptor 9
keywords: Colorectal cancer; DNA-based immunomodulatory sequences; Inflammatory bowel diseases; Synthetic oligodeoxynucleotide sequences; Toll-like receptor 9