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Type I IL-1 receptor mediates IL-1 and intracellular IL-1 receptor antagonist effects in skin inflammation.
Journal article

Type I IL-1 receptor mediates IL-1 and intracellular IL-1 receptor antagonist effects in skin inflammation.

  • 2007-05-04
Published in:
  • The Journal of investigative dermatology. - 2007
Animals
Dermatitis
Interleukin 1 Receptor Antagonist Protein
Interleukin-1
Mice
Mice, Inbred DBA
Mice, Knockout
Protein Isoforms
RNA, Messenger
Receptors, Interleukin-1
Skin
Tetradecanoylphorbol Acetate
English The IL-1 system plays a key role in skin physiology and pathology. In this study, we used mutant mice lacking the type I IL-1 receptor (IL-1RI), lacking IL-1 receptor antagonist (IL-1Ra), or overexpressing the human intracellular (ic) IL-1Ra1 isoform, as well as combinations thereof, to dissect the role of the IL-1 system in phorbol 13-myristate 12-acetate (PMA)-induced skin inflammation. In wild-type (WT) mice, PMA application induced epidermal thickening and dermal inflammation. Skin IL-1alpha production and circulating levels of the acute-phase protein serum amyloid A (SAA) were elevated. In mice lacking IL-1RI or overexpressing icIL-1Ra1, PMA induced similar epidermal thickening as in WT mice, but dermal inflammation was partially prevented. Skin IL-1alpha mRNA expression was similar in PMA-treated IL-1RI-/- and WT mice, whereas the increase in serum SAA was suppressed in IL-1RI-/- mice. Interestingly, PMA-induced IL-1alpha mRNA expression was further enhanced by icIL-1Ra1 overexpression in an IL-1RI-dependent manner. Finally, IL-1Ra-/- mice spontaneously displayed skin lesions characterized by high IL-1beta, but not IL-1alpha, expression. In conclusion, PMA-induced epidermal thickening and skin IL-1alpha expression were independent of IL-1 signaling, in contrast to dermal inflammation and systemic inflammatory response.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/220057
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