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- Title
Oligodeoxynucleotides inhibit Toll-like receptor 3 mediated cytotoxicity and CXCL8 release in keratinocytes.
- Authors
Grimstad, Øystein; Pukstad, Brita; Stenvik, Jørgen; Espevik, Terje
- Abstract
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.
- Subjects
KERATINOCYTES; VIRUS diseases; NUCLEOTIDES; CELL-mediated cytotoxicity; CELLULAR control mechanisms
- Publication
Experimental Dermatology, 2012, Vol 21, Issue 1, p7
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/j.1600-0625.2011.01390.x