Capsaicin attenuates the effect of inflammatory cytokines in a HaCaT cell model for basal keratinocytes

Maria Fernanda Cervantes Recalde; Jana Schmidt; Cristina Girardi; Marco Massironi; Markus Leo Rechl; Joachim Hans; Dominik Stuhlmann; Veronika Somoza; Barbara Lieder

doi:10.3389/fphar.2024.1474898

Capsaicin attenuates the effect of inflammatory cytokines in a HaCaT cell model for basal keratinocytes

Front Pharmacol. 2024 Oct 14:15:1474898. doi: 10.3389/fphar.2024.1474898. eCollection 2024.

Authors

Maria Fernanda Cervantes Recalde^{1

2}, Jana Schmidt¹, Cristina Girardi³, Marco Massironi³, Markus Leo Rechl^{1

2

4}, Joachim Hans⁵, Dominik Stuhlmann⁵, Veronika Somoza^{1

6}, Barbara Lieder^{1

4

7}

Affiliations

¹ Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
² Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, Vienna, Austria.
³ Symrise Srl, CUTECH, Padova, Italy.
⁴ Christian Doppler Laboratory for Taste Research, Faculty of Chemistry, University of Vienna, Vienna, Austria.
⁵ Symrise AG, Holzminden, Germany.
⁶ Leibniz Institute of Food Systems Biology, Technical University of Munich, Freising, Germany.
⁷ Institute of Clinical Nutrition, University of Hohenheim, Stuttgart, Germany.

Abstract

Introduction: The resolution of the skin's inflammatory response is only possible if its barrier function is restored. TRPV1 channel activation plays an important role during inflammation but the effect of this activation on the skin barrier under inflammatory conditions has not been clarified. We hypothesize that it could potentially aid the keratinocyte barrier by reducing inflammatory cytokine release and promoting tight junction development.

Methods: To explore the role of TRPV1 activation in inflammation, we designed and optimized an in vitro model of keratinocytes with basal epidermal layer characteristics using HaCaT cells and TNFα to induce inflammation.

Results: TNFα increased the gene expression of tight junction protein claudin 1 (CLDN1) by at least 2.60 ± 0.16-fold, in a concentration-dependent manner, over a 48 h period. The administration of a capsaicin pre-treatment reduced the CLDN1 expression to 1.51 ± 0.16-fold during the first 6 h after TNFα induction, whereas IL-8 cytokine release was reduced 0.64 ± 0.17-fold. After 48 h, CLDN1 protein levels increased by a factor of 6.57 ± 1.39 compared to cells only treated with TNFα.

Discussion: These results suggest that activation of TRPV1 by capsaicin can potentiate the increase in CLDN1 expression and CLDN1 protein synthesis induced by TNFα in cultured keratinocytes, while reducing the release of IL-8.

Keywords: TRPV1; capsaicin; inflammation; permeability; skin.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by Symrise AG. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.