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Title

The severity of imiquimod-induced mouse skin inflammation is independent of endogenous IL-38 expression

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Published in PLOS ONE. 2018, vol. 13, no. 3, p. e0194667
Abstract The IL-1 cytokine family includes eleven members, among which Il-36α, β and γ, IL-36Ra and IL-38. The IL-36 cytokines are involved in the pathogenesis of psoriasis. IL-38 is also expressed in the skin and was previously proposed to act as an IL-36 antagonist. In this study, we thus examined expression and function of Il-38 in a mouse model of imiquimod (IMQ)-induced skin inflammation. Il-38 mRNA was detected in the epidermis and in primary mouse keratinocytes, but not in dermal fibroblasts. At the peak of IMQ-induced inflammation, skin Il-38 mRNA levels were reduced, whereas Il-36ra mRNA expression increased. The severity of IMQ-induced skin inflammation, as assessed by recording ear thickness and histological changes, was similar in Il-38 KO and WT littermate control mice, while, in contrast, Il-36ra-deficient mice displayed more severe skin pathology than their WT littermates. Il-38-deficiency had no impact on IMQ-induced expression of proinflammatory mediators in the skin in vivo, on the basal expression of various cytokines or chemokines by cultured primary keratinocytes and dermal fibroblasts in vitro, or on the response of these cells to Il-36β. Finally, after cessation of topical IMQ application, the resolution of skin inflammation was also not altered in Il-38 KO mice. In conclusion, Il-38-deficiency did not impact the development or resolution of IMQ-induced skin inflammation. Our observations further suggest that endogenous Il-38 does not exert Il-36 inhibitory activity in this model, or in cultured skin cells. A potential anti-inflammatory function of Il-38 in mouse skin thus still remains to be demonstrated.
Keywords AminoquinolinesAnimalsCellsCulturedDermatitis/genetics/metabolism/pathologyDisease ModelsAnimalDrug Eruptions/genetics/metabolism/pathologyFemaleInflammation/chemically induced/genetics/pathologyInterleukin-1/genetics/metabolismInterleukins/genetics/metabolismMiceMiceInbred BALB CMiceInbred C57BLMiceKnockoutSeverity of Illness IndexSkin/metabolism/pathology
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PMID: 29554104
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Article (Author postprint) (3.3 MB) - public document Free access
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Research group Mécanisme de l'inflammation articulaire (44)
Projects Rheumasearch Foundation
Institute of Arthritis Research
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(ISO format)
PALOMO, Jennifer et al. The severity of imiquimod-induced mouse skin inflammation is independent of endogenous IL-38 expression. In: PLOS ONE, 2018, vol. 13, n° 3, p. e0194667. https://archive-ouverte.unige.ch/unige:110101

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Deposited on : 2018-10-30

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