Epidermal Expression and Regulation of Interleukin-33 during Homeostasis and Inflammation: Strong Species Differences.
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.
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.
Olav
O
Sundnes
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.
Wojciech
W
Pietka
Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway.
Tamara
T
Loos
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.
Jon
J
Sponheim
Department of Immunology, Merck Research Laboratories (formerly Schering-Plough Biopharma/DNAX), Palo Alto, California, USA.
Andrew L
AL
Rankin
Department of Immunology, Merck Research Laboratories (formerly Schering-Plough Biopharma/DNAX), Palo Alto, California, USA.
Stefan
S
Pflanz
Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway.
Vibeke
V
Bertelsen
Department of Dermatology, University of Oslo and Oslo University Hospital, Oslo, Norway.
Jan C
JC
Sitek
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.
Johanna
J
Hol
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.
Guttorm
G
Haraldsen
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.
Denis
D
Khnykin
D000328:Adult; D000818:Animals; D001707:Biopsy, Needle; D015153:Blotting, Western; D003872:Dermatitis / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics* / Q000503:physiopathology; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012494:Sampling Studies; D013045:Species Specificity; D034421:Sus scrofa; D013552:Swine; D046509:Tissue Culture Techniques
C506536:IL33 protein, human; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins