Induction of acute phase response genes in keratinocytes following exposure to oligodeoxynucleotides.
Keratinocytes have the ability to take up oligodeoxynucleotides (ODN) and plasmid DNA probably by receptor-mediated endocytosis. Despite the use of DNA for antisense and gene therapy little is known about the regulation of genes following exposure to nucleic acids. To systematically identify gene regulation in keratinocytes upon exposure to ODN we screened human cytokine DNA arrays containing 383 different genes and found interleukin (IL) 1alpha, IL-1beta, integrin-beta(1), alpha-tubulin, and follistatin highly induced, while most genes were unaffected. The time course and concentration dependence for IL-1alpha and follistatin expression were analyzed by standard northern blot technique. ODN of different length and sequence induced comparable amounts of IL-1alpha and follistatin. Their induction was independent of negative charge and of several proinflammatory compounds such as lipopolysaccharides, IL-1beta, and interferon-gamma but was partly inhibited by activin A. In summary, our study revealed several genes of the acute phase protein family that are induced in a non-sequence-specific manner following the exposure of normal human keratinocytes to ODN. Therefore it is tempting to speculate that upon internalization ODN bind to an intracellular receptor (e.g., Toll-like receptor 9) which mediates signaling.
Mirmohammadsadegh
Alireza
A
Department of Dermatology, Venerology and Allergology, University of Essen, Hufelandstrasse 55, 45122 Essen, Essen, Germany.
Maschke
Jan
J
Basner-Tschakarjan
Etiena
E
Bär
Annett
A
Hengge
Ulrich R
UR
D000209:Acute-Phase Proteins / Q000187:drug effects / Q000235:genetics / Q000494:pharmacology; D000210:Acute-Phase Reaction / Q000235:genetics*; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D038681:Follistatin / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D019012:Integrin beta1 / Q000187:drug effects / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D014404:Tubulin / Q000187:drug effects / Q000235:genetics
D000209:Acute-Phase Proteins; D016207:Cytokines; D038681:Follistatin; D019012:Integrin beta1; D007375:Interleukin-1; D009838:Oligodeoxyribonucleotides; D014404:Tubulin