Full length interleukin 33 aggravates radiation-induced skin reaction

Kurow, O. et al. (2017) Full length interleukin 33 aggravates radiation-induced skin reaction. Frontiers in Immunology, 8, 722. (doi:10.3389/fimmu.2017.00722) (PMID:28702024) (PMCID:PMC5487387)

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Abstract

The interleukin (IL)-1 family member IL-33 has been described as intracellular alarmin with broad roles in wound healing, skin inflammation but also autoimmunity. Its dichotomy between full length (fl) IL-33 and the mature (m) form of IL-33 and its release by necrosis is still not fully understood. Here, we compare functional consequences of both forms in the skin in vivo, and therefore generated two lines of transgenic mice which selectively overexpress mmIL-33 and flmIL-33 in basal keratinocytes. Transgene mRNA was expressed at high level in skin of both lines but not in organs due to the specific K14 promoter. We could demonstrate that transgenic overexpression of mmIL-33 in murine keratinocytes leads to a spontaneous skin inflammation as opposed to flmIL-33. K14-mmIL-33 mice synthesize and secrete high amounts of mmIL-33 along with massive cutaneous manifestations, like increased epidermis and dermis thickness, infiltration of mast cells in the epidermis and dermis layers and marked hyperkeratosis. Using skin inflammation models such as IL-23 administration, imiquimod treatment, or mechanical irritation did not lead to exacerbated inflammation in the K14-flmIL-33 strain. As radiation induces a strong dermatitis due to apoptosis and necrosis, we determined the effect of fractionated radiation (12 Gy, 4 times). In comparison to wild-type mice, an increase in ear thickness in flmIL-33 transgenic mice was observed 25 days after irradiation. Macroscopic examination showed more severe skin symptoms in irradiated ears compared to controls. In summary, secreted mmIL-33 itself has a potent capacity in skin inflammation whereas fl IL-33 is limited due to its intracellular retention. During tissue damage, fl IL-33 exacerbated radiation-induced skin reaction.

Item Type:Articles
Keywords:Dermatitis, interleukin-33, necrosis, radiation, skin inflammation.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Gilchrist, Dr Derek
Authors: Kurow, O., Frey, B., Schuster, L., Schmitt, V., Adam, S., Hahn, M., Gilchrist, D., McInnes, I. B., Wirtz, S., Gaipl, U. S., Krönke, G., Schett, G., Frey, S., and Hueber, A. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Frontiers in Immunology
Publisher:Frontiers Media
ISSN:1664-3224
ISSN (Online):1664-3224
Copyright Holders:Copyright © 2017 Kurow, Frey, Schuster, Schmitt, Adam, Hahn, Gilchrist, McInnes, Wirtz, Gaipl, Krönke, Schett, Frey and Hueber.
First Published:First published in Frontiers in Immunology 8: 722
Publisher Policy:Reproduced under a Creative Commons license

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