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J Invest Dermatol. 2015 Jul;135(7):1771-1780. doi: 10.1038/jid.2015.85. Epub 2015 Mar 4.

Epidermal Expression and Regulation of Interleukin-33 during Homeostasis and Inflammation: Strong Species Differences.

Author information

1
K.G.Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital, Oslo, Norway; Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway.
2
Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway.
3
Department of Immunology, Merck Research Laboratories (formerly Schering-Plough Biopharma/DNAX), Palo Alto, California, USA.
4
Department of Dermatology, University of Oslo and Oslo University Hospital, Oslo, Norway.
5
K.G.Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital, Oslo, Norway; Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: gharalds@rr-research.no.

Abstract

IL-33 is a novel IL-1 family member with a putative role in inflammatory skin disorders and a complex biology. Therefore, recent conflicting data regarding its function in experimental models justify a close assessment of its tissue expression and regulation. Indeed, we report here that there are strong species differences in the expression and regulation of epidermal IL-33. In murine epidermis, IL-33 behaved similar to an alarmin, being constitutively expressed in keratinocyte nuclei and rapidly lost during acute inflammation. By contrast, human and porcine IL-33 were weakly expressed or absent in keratinocytes of noninflamed skin but induced during acute inflammation. To this end, we observed that expression of IL-33 in human keratinocytes but not murine keratinocytes was strongly induced by IFN-γ, and this upregulation completely depended on the presence of EGFR ligands. Accordingly, IFN-γ increased the expression of IL-33 in the basal layers of the epidermis in human ex vivo skin cultures only, despite good evidence of IFN-γ activity in cultures from both species. Together these findings demonstrate that a full understanding of IL-33 function in clinical settings must take species-specific differences into account.

PMID:
25739051
DOI:
10.1038/jid.2015.85
[Indexed for MEDLINE]
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