title: The expression and function of Toll-like receptors 3 and 9 in human colon carcinoma.
abstract: Toll-like receptors (TLRs) are pattern-recognition receptors that are important in immune signaling. TLR recognition of various viral components including double-stranded RNA (TLR3) and unmethylated CpG-DNA (TLR9) plays a crucial role in cell survival. However, TLR expression and function in colon carcinoma cells are not well clarified. We investigated the expression of TLR3 and TLR9 in colon carcinoma cells using immunohistochemical methods. The function of TLR3 and TLR9 signaling in carcinoma cell lines was studied by direct cell stimulation with, or by cell transfection of, polyinosinic-polycytidylic acid (Poly I:C), a synthetic form of dsRNA, and by cell stimulation with CpG-oligodeoxynucleotides (ODNs), respectively. Positive TLR3 and TLR9 immunohistochemical staining was observed in 91 and 86% of human hepatocellular carcinoma (HCC) tissues, respectively. Cell surface stimulation of TLR3 with Poly I:C did not affect cell viability but it did activate NF-κB activity. By contrast, stimulation of intracellular TLRs with transfected Poly I:C significantly induced apoptosis. Cell surface stimulation of TLR9 with CpG-ODNs promoted cell proliferation, and, furthermore, these CpG-ODN TLR9 agonists reduced the cytotoxicity of the anticancer drug adriamycin. Cell surface expression of TLR3 and TLR9 in colon carcinoma cells plays an important role in cell survival. In addition, the proapoptotic activity of intracellularly expressed TLR3 may provide the possibility of using TLR3 agonists as novel clinical cytotoxic agents against colon carcinoma cells.
authors: Department of Internal Medicine, Mie Graduate University School of Medicine, Tsu, Mie 514-8507, Japan.
authors: Keiichiro
authors: K
authors: Nojiri
authors: Kazushi
authors: K
authors: Sugimoto
authors: Katsuya
authors: K
authors: Shiraki
authors: Masahiko
authors: M
authors: Tameda
authors: Yuuji
authors: Y
authors: Inagaki
authors: Satoko
authors: S
authors: Kusagawa
authors: Suguru
authors: S
authors: Ogura
authors: Junichiro
authors: J
authors: Tanaka
authors: Misao
authors: M
authors: Yoneda
authors: Norihiko
authors: N
authors: Yamamoto
authors: Hiroshi
authors: H
authors: Okano
authors: Yoshiyuki
authors: Y
authors: Takei
authors: Masaaki
authors: M
authors: Ito
authors: Chika
authors: C
authors: Kasai
authors: Hidekazu
authors: H
authors: Inoue
authors: Koujiro
authors: K
authors: Takase
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; C495344:TLR3 protein, human; C495371:TLR9 protein, human; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D004317:Doxorubicin; D011070:Poly I-C