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Oligodeoxynucleotides inhibit Toll‐like receptor 3 mediated cytotoxicity and CXCL8 release in keratinocytes
Author(s) -
Grimstad Øystein,
Pukstad Brita,
Stenvik Jørgen,
Espevik Terje
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2011.01390.x
Subject(s) - tlr3 , proinflammatory cytokine , cytotoxicity , toll like receptor , receptor , chemistry , chemokine , immunology , pharmacology , microbiology and biotechnology , biology , inflammation , innate immune system , biochemistry , in vitro
Toll‐like receptor 3 (TLR3) is an important sensor of viral infections and injury of 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 of the alarmin high‐mobility group protein B1 and reduced responses in a MTT‐assay. PolyI:C was a potent inducer of proinflammatory cytokines, and both these responses and the cytotoxic effects were found to be TLR3 dependent, as demonstrated by the use of siRNA for TLR3. Interestingly, co‐stimulation with oligodeoxynucleotides (ODNs) inhibited all polyI:C induced effects. This inhibition was found to be mediated by the competition of endocytic uptake of polyI:C and ODNs. We have found polyI:C induced cytotoxicity and proinflammatory responses to be dependent of TLR3 and that this may be inhibited by ODNs. With these findings, we see a promising potential for ODNs in inhibiting TLR3‐induced responses in inflammatory skin disorders.