Format

Send to

Choose Destination
J Invest Dermatol. 2019 Jan;139(1):81-90. doi: 10.1016/j.jid.2018.07.023. Epub 2018 Aug 16.

Hypo-osmotic Stress Drives IL-33 Production in Human Keratinocytes-An Epidermal Homeostatic Response.

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 Oral Biology, University of Oslo and Oslo University Hospital, Oslo, Norway.
4
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.
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; Department of Rheumatology, Dermatology and Infectious Diseases, University of Oslo and Oslo University Hospital, Oslo, Norway.

Abstract

Although inflammation has traditionally been considered a response to either exogenous pathogen-associated signals or endogenous signals of cell damage, other perturbations of homeostasis, generally referred to as stress, may also induce inflammation. The relationship between stress and inflammation is, however, not well defined. Here, we describe a mechanism of IL-33 induction driven by hypo-osmotic stress in human keratinocytes and also report interesting differences when comparing the responsiveness of other inflammatory mediators. The induction of IL-33 was completely dependent on EGFR and calcium signaling, and inhibition of calcium signaling not only abolished IL-33 induction but also dramatically changed the transcriptional pattern of other cytokines upon hypo-osmotic stress. IL-33 was not secreted but instead showed nuclear sequestration, conceivably acting as a failsafe mechanism whereby it is induced by potential danger but released only upon more extreme homeostatic perturbations that result in cell death. Finally, stress-induced IL-33 was also confirmed in an ex vivo human skin model, translating this mechanism to a potential tissue-relevant signal in the human epidermis. In conclusion, we describe hypo-osmotic stress as an inducer of IL-33 expression, linking cellular stress to nuclear accumulation of a strong proinflammatory cytokine.

PMID:
30120934
DOI:
10.1016/j.jid.2018.07.023

Supplemental Content

Full text links

Icon for Elsevier Science Icon for Norwegian BIBSYS system
Loading ...
Support Center