TLR5-mediated phosphoinositide 3-kinase activation negatively regulates flagellin-induced proinflammatory gene expression

Journal of Immunology

Volumn 176, Issue 10, 2006, Pages 6194-6201

  Yu, Yimin ^a   Nagai, Shigenori ^b,c   Wu, Huixia ^a   Neish, Andrew S ^a   Koyasu, Shigeo ^b,c   Gewirtz, Andrew T ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^c JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; FLAGELLIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 6; INTERLEUKIN 8; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE P38; NITRITE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B; TOLL LIKE RECEPTOR 5; WORTMANNIN;

ARTICLE; BLOOD LEVEL; CELL STIMULATION; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; EPITHELIUM CELL; GENE EXPRESSION REGULATION; GENE INDUCTION; HETEROZYGOTE; HUMAN; HUMAN CELL; INFLAMMATION; KNOCKOUT MOUSE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION;

EID: 33646471083     PISSN: 00221767     EISSN: None     Source Type: Journal    
DOI: 10.4049/jimmunol.176.10.6194     Document Type: Article

References (27)

1. Akira, S., and K. Takeda. 2004. Toll-like receptor signalling. Nat. Rev. Immunol. 4:499-511.
2. Gewirtz, A. T. 2003. Intestinal epithelial Toll-like receptors: to protect. And serve? Curr. Pharm. Des. 9: 1-5.
3. Hayashi, F., K. D. Smith, A. Ozinsky, T. R. Hawn, E. C. Yi, D. R. Goodlett, J. K. Eng, S. Akira, D. M. Underhill, and A. Aderem. 2001. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410: 1099-1103.
4. Gewirtz, A. T., T. A. Navas, S. Lyons, P. J. Godowski, and J. L. Madara. 2001. Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J. Immunol. 167: 1882-1885.
5. Yu, Y., H. Zeng, S. Lyons, A. Carlson, D. Merlin, A. S. Neish, and A. T. Gewirtz. 2003. TLR5-mediated activation of p38 MAPK regulates epithelial IL-8 expression via posttranscriptional mechanism. Am. J. Physiol. 285: G282-G290.
6. Toshchakov, V., B. W. Jones, P. Y. Perera, K. Thomas, M. J. Cody, S. Zhang, B. R. Williams, J. Major, T. A. Hamilton, M. J. Fenton, and S. N. Vogel. 2002. TLR4, but not TLR2, mediates IFN-β-induced STAT1α/β- dependent gene expression in macrophages. Nat. Immunol. 3: 392-398.
7. Yu, Y., H. Zeng, M. Vijay-Kumar, A. S. Neish, D. Merlin, S. V. Sitaraman, and A. T. Gewirtz. 2004. STAT signaling underlies difference between flagellin-induced and tumor necrosis factor-α-induced epithelial gene expression. J. Biol. Chem. 279: 35210-35218.
8. Horng, T., G. M. Barton, R. A. Flavell, and R. Medzhitov. 2002. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420: 329-333.
9. Elliott, J., and J. A. Johnston. 2004. SOCS: role in inflammation, allergy and homeostasis. Trends Immunol. 25: 434-440.
10. Kobayashi, K., L. D. Hernandez, J. E. Galan, C. A. Janeway, Jr., R. Medzhitov, and R. A. Flavell. 2002. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110: 191-202.
11. Fukao, T., and S. Koyasu. 2003. PI3K and negative regulation of TLR signaling. Trends Immunol. 24: 358-363.
12. Fukao, T., M. Tanabe, Y. Terauchi, T. Ota, S. Matsuda, T. Asano, T. Kadowaki, T. Takeuchi, and S. Koyasu. 2002. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat. Immunol. 3: 875-881.
13. Arbibe, L., J. P. Mira, N. Teusch, L. Kline, M. Guha, N. Mackman, P. I. Godowski, R. J. Ulevitch, and U. G. Knaus. 2000. Toll-like receptor 2-mediated NF-κB activation requires a Rac1-dependent pathway. Nat. Immunol. 1: 533-540.
14. Sarkar, S. N., K. L. Peters, C. P. Elco, S. Sakamoto, S. Pal, and G. C. Sen. 2004. Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling. Nat. Struct. Mol. Biol. 11: 1060-1067.
15. Park, Y., S. W. Lee, and Y. C. Sung. 2002. Cutting edge: CpG DNA inhibits dendritic cell apoptosis by up-regulating cellular inhibitor of apoptosis proteins through the phosphatidylinositide-3′-OH kinase pathway. J. Immunol. 168: 5-8.
16. Gewirtz, A. T., K. A. Reed, D. Merlin, A. S. Neish, and J. L. Madara. 2002. Modeling microbial-epithelial interactions in the intestine. Methods Microbiol. 31: 377-396.
17. Gewirtz, A. T., P. O. Simon, Jr., C. K. Schmitt, L. J. Taylor, C. H. Hagedorn, A. D. O'Brien, A. S. Neish, and J. L. Madara. 2001. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. J. Clin. Invest. 107: 99-109.
18. + T cells in vivo. J. Immunol. 169: 3914-3919.
19. Gouraud, S., A. Laera, G. Calamita, M. Carmosino, G. Procino, O. Rossetto, R. Mannucci, W. Rosenthal, M. Svelto, and G. Valenti. 2002. Functional involvement of VAMP/synaptobrevin-2 in cAMP-stimulated aquaporin 2 translocation in renal collecting duct cells. J. Cell Sci. 115: 3667-3674.
20. Suzuki, H., Y. Terauchi, M. Fujiwara, S. Aizawa, Y. Yazaki, T. Kadowaki, and S. Koyasu. 1999. Xid-like immunodeficiency in mice with disruption of the p85α subunit of phosphoinositide 3-kinase. Science 283: 390-392.
21. Tibbles, L. A., Y. L. Ing, F. Kiefer, J. Chan, N. Iscove, J. R. Woodgett, and N. J. Lassam. 1996. MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6. EMBO J. 15: 7026-7035.
22. Sanders, C. J., D. A. Moore, I. R. Williams, and A. T. Gewirtz. 2005. Non-hematopoietic cells link innate and adaptive immune responses to bacterial flagellin via early cytokine production. FASEB J. 19: A939.
23. Abreu, M. T., and M. Arditi. 2004. Innate immunity and Toll-like receptors: clinical implications of basic science research. J. Pediatr. 144: 421-429.
24. Kontoyiannis, D., M. Pasparakis, T. T. Pizarro, F. Cominelli, and G. Kollias. 1999. Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity 10: 387-398.
25. Zeng, H., H. Wu, V. Sloane, R. Jones, Y. Yu, P. Lin, A. T. Gewirtz, and A. S. Neish. 2005. Flagellin/TLR5 responses in epithelia reveal intertwined activation of inflammatory and apoptotic pathways. Am. J. Physiol. 290: G96-G108.
26. WAF1/CIP1 induction via p38 mitogen-activated protein kinase. Gastroenterology 129: 1875-1888.
27. Gewirtz, A. T., M. Vijay-Kumar, S. R. Brant, R. H. Duerr, D. L. Nicolae, and J. H. Cho. 2006. Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease. Am. J. Physiol. In press.