Oligodeoxynucleotides inhibit Toll-like receptor 3 mediated cytotoxicity and CXCL8 release in keratinocytes.

作者: Øystein Grimstad , Brita Pukstad , Jørgen Stenvik , Terje Espevik

DOI: 10.1111/J.1600-0625.2011.01390.X

关键词: Cytotoxic T cellCell cultureCytotoxicityProinflammatory cytokineToll-like receptorMolecular biologyTLR3ReceptorPharmacologyBiologyInterleukin 8

摘要: Toll-like receptor 3 (TLR3) is an important sensor of viral infections and injury self in keratinocytes. In this study, we stimulated primary keratinocytes with the TLR3-ligand polyI:C. This induced a toxic effect shown by up-regulation alarmin high-mobility group protein B1 reduced responses MTT-assay. PolyI:C was potent inducer proinflammatory cytokines, both these cytotoxic effects were found to be TLR3 dependent, as demonstrated use siRNA for TLR3. Interestingly, co-stimulation oligodeoxynucleotides (ODNs) inhibited all polyI:C effects. inhibition mediated competition endocytic uptake ODNs. We have cytotoxicity dependent that may With findings, see promising potential ODNs inhibiting TLR3-induced inflammatory skin disorders.

参考文章(35)
Ruslan Medzhitov, Paula Preston-Hurlburt, Charles A. Janeway, A human homologue of the Drosophila Toll protein signals activation of adaptive immunity Nature. ,vol. 388, pp. 394- 397 ,(1997) , 10.1038/41131
Kyung Ho Lee, Kyung-Ah Cho, Ji-Yoon Kim, Jin-Young Kim, Ji-Hae Baek, So-Youn Woo, Jin-Woo Kim, Filaggrin knockdown and Toll-like receptor 3 (TLR3) stimulation enhanced the production of thymic stromal lymphopoietin (TSLP) from epidermal layers. Experimental Dermatology. ,vol. 20, pp. 149- 151 ,(2011) , 10.1111/J.1600-0625.2010.01203.X
Øystein Grimstad, Øystein Sandanger, Liv Ryan, Kari Otterdal, Jan Kristian Damaas, Brita Pukstad, Terje Espevik, Cellular sources and inducers of cytokines present in acute wound fluid Wound Repair and Regeneration. ,vol. 19, pp. 337- 347 ,(2011) , 10.1111/J.1524-475X.2011.00668.X
Bruno Salaun, Isabelle Coste, Marie-Clotilde Rissoan, Serge J. Lebecque, Toufic Renno, TLR3 can directly trigger apoptosis in human cancer cells. Journal of Immunology. ,vol. 176, pp. 4894- 4901 ,(2006) , 10.4049/JIMMUNOL.176.8.4894
Erik A. L. Biessen, Helene Vietsch, Johan Kuiper, Martin K. Bijsterbosch, Theo J. C. van Berkel, Liver Uptake of Phosphodiester Oligodeoxynucleotides Is Mediated by Scavenger Receptors Molecular Pharmacology. ,vol. 53, pp. 262- 269 ,(1998) , 10.1124/MOL.53.2.262
Takashi Sato, Masaki Yamamoto, Takeshi Shimosato, Dennis M. Klinman, Accelerated wound healing mediated by activation of Toll-like receptor 9. Wound Repair and Regeneration. ,vol. 18, pp. 586- 593 ,(2010) , 10.1111/J.1524-475X.2010.00632.X
Michael T. Lotze, Herbert J. Zeh, Anna Rubartelli, Louis J. Sparvero, Andrew A. Amoscato, Newell R. Washburn, Michael E. DeVera, Xiaoyan Liang, Mahmut Tör, Timothy Billiar, The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity Immunological Reviews. ,vol. 220, pp. 60- 81 ,(2007) , 10.1111/J.1600-065X.2007.00579.X
Paola Scaffidi, Tom Misteli, Marco E. Bianchi, Release of chromatin protein HMGB1 by necrotic cells triggers inflammation Nature. ,vol. 418, pp. 191- 195 ,(2002) , 10.1038/NATURE00858