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

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.