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Sökning: WFRF:(Ohlsson Anna) > (2020-2024) > Effect of IFN-γ on ...

Effect of IFN-γ on the kynurenine/tryptophan ratio in monolayer-cultured keratinocytes and a 3D reconstructed human epidermis model

Gustafsson, Anna (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
Prgomet, Zdenka (författare)
Malmö universitet,Odontologiska fakulteten (OD)
Jankovskaja, Skaidre (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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Ruzgas, Tautgirdas (författare)
Malmö universitet,Biofilms Research Center for Biointerfaces,Institutionen för biomedicinsk vetenskap (BMV)
Engblom, Johan (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
Ohlsson, Lars (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
Gjörloff Wingren, Anette (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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 (creator_code:org_t)
Japanese Society for Investigative Dermatology, 2020
2020
Engelska.
Ingår i: Journal of dermatological science (Amsterdam). - : Japanese Society for Investigative Dermatology. - 0923-1811 .- 1873-569X. ; 99:3, s. 177-184
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • BACKGROUND: Interferon-gamma (IFN-γ) represents a potent inducer for keratinocyte inflammatory and immune activation in vitro. Since tryptophan (trp) conversion to kynurenine (kyn) is involved in inflammation, the topical kyn/trp ratio may serve as a biomarker of skin inflammation. However, the trp metabolism in keratinocytes exposed to IFN-γ is not yet fully understood.OBJECTIVE: The aim of this study was to establish a human epidermis model in order to quantify cytokine and kyn/trp secretion from IFN-γ stimulated cells and tissues. Moreover, to compare the cell response of 2D-cultured keratinocytes and the 3D epidermis model.METHODS: Polycarbonate filters were used on which primary keratinocytes could attach and stratify in order to form the typical layers of reconstructed human epidermis (RHE). After IFN-γ treatment, secretion of kyn/trp was measured by high performance liquid chromatography. Gene and protein expression of indoleamine 2,3-dioxygenase 1 (IDO) was analyzed with real-time PCR and immunohistochemistry. The secretion of cytokines was quantified with ELISA.RESULTS: Trp catabolism to kyn was significantly increased (P < 0.01) in the 2D culture in response to IFN-γ treatment. Before kyn secretion, IDO was strongly upregulated (P < 0.001). IFN-γ treatment also increased the secretion of IL-6 and IL-8 from the keratinocytes. In the RHE, IDO was upregulated by IFN-γ, and kyn secretion could be detected. Interestingly, IDO expression was only present in the basal cells of the RHE.CONCLUSION: Our results suggest that IFN-γ acts as an inducer of trp degradation preferentially in undifferentiated keratinocytes, indicated by the IDO expression in the basal layer of the RHE.

Nyckelord

IDO
Kynurenine
Pro-inflammatory cytokines
Reconstructed human epidermis
Tryptophan

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