Type I IL-1 receptor mediates IL-1 and intracellular IL-1 receptor antagonist effects in skin inflammation.
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.
Palmer
Gaby
G
Division of Rheumatology, University Hospital, Geneva, Switzerland.
Talabot-Ayer
Dominique
D
Kaya
Gürkan
G
Gabay
Cem
C
D000818:Animals; D003872:Dermatitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000502:physiology*; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D012867:Skin / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D020033:Protein Isoforms; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D013755:Tetradecanoylphorbol Acetate