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Sphingosine-1-phosphate exhibits anti-proliferative and anti-inflammatory effects in mouse models of psoriasis

  • Background: It has been indicated that the sphingolipid sphingosine-1-phosphate (SIP) restrains the ability of dendritic cells to migrate to lymph nodes. Furthermore SIP has been demonstrated to inhibit cell growth in human keratinocytes. However, only little is known about the effect of S1P in hyperproliferative and inflammatory in vivo models. Objective: In this study, locally acting SIP was explored in different experimental mouse models of psoriasis vulgaris. Methods: S1P and FTY720 were tested in the imiquimod-induced psoriasis mouse model, the mouse tail assay and a pilot study of the severe combined immunodeficiency mice (SCID). Results: In the imiquimod model the positive control diflorasone diacetate and S1P, but not FTY720 reduced the imiquimod-induced epidermal hyperproliferation of the ear skin. This effect was confirmed in the SCID model, where S1P treated skin from patients suffering from psoriasis showed a decrease in epidermal thickness compared to vehicle. In the imiquimod model, there was also significantBackground: It has been indicated that the sphingolipid sphingosine-1-phosphate (SIP) restrains the ability of dendritic cells to migrate to lymph nodes. Furthermore SIP has been demonstrated to inhibit cell growth in human keratinocytes. However, only little is known about the effect of S1P in hyperproliferative and inflammatory in vivo models. Objective: In this study, locally acting SIP was explored in different experimental mouse models of psoriasis vulgaris. Methods: S1P and FTY720 were tested in the imiquimod-induced psoriasis mouse model, the mouse tail assay and a pilot study of the severe combined immunodeficiency mice (SCID). Results: In the imiquimod model the positive control diflorasone diacetate and S1P, but not FTY720 reduced the imiquimod-induced epidermal hyperproliferation of the ear skin. This effect was confirmed in the SCID model, where S1P treated skin from patients suffering from psoriasis showed a decrease in epidermal thickness compared to vehicle. In the imiquimod model, there was also significant inhibition of ear swelling and a moderate reduction of inflammatory cell influx and oedema formation in ear skin by SIP treatment. The inflammatory response on the back skin was, however, only reduced by diflorasone diacetate. In the mouse tail assay, the influence of S1P and FTY720 in stratum granulosum formation was tested compared to the positive control calcipotriol. Whereas topical administration of calcipotriol led to a low but significant increase of stratum granulosum, S1P and FTY720 lacked such an effect. Conclusion: Taken together, these results imply that topical administration of SIP might be a new option for the treatment of mild to moderate psoriasis lesions.show moreshow less

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Author details:Katrin Schaper, Jeannette Dickhaut, Lukasz JaptokGND, Manfred Kietzmann, Reinhard Mischke, Burkhard KleuserORCiDGND, Wolfgang Bäumer
DOI:https://doi.org/10.1016/j.jdermsci.2013.03.006
ISSN:0923-1811
Title of parent work (English):Journal of dermatological scienc
Publisher:Elsevier
Place of publishing:Clare
Publication type:Article
Language:English
Year of first publication:2013
Publication year:2013
Release date:2017/03/26
Tag:Imiquimod; Psoriasis; SCID mice; Sphingosine-1-phosphate
Volume:71
Issue:1
Number of pages:8
First page:29
Last Page:36
Funding institution:Hannoversche Gesellschaft zur Forderung der Kleintiermedizin e.V.
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
Peer review:Referiert
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