| Autor: |
Rademacher, Franziska, Scheel, Annika, Gläser, Regine, Schröder, Lena, Heinemann, Nina, Bartels, Joachim, Gerdes, Sascha, Stölzl, Dora, Rodriguez, Elke, Döhner, Katinka, Weidinger, Stephan, Werfel, Thomas, Harder, Jürgen |
| Předmět: |
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| Zdroj: |
Allergy; Jun2024, Vol. 79 Issue 6, p1573-1583, 11p |
| Abstrakt: |
Background: The antimicrobial ribonuclease RNase 7 is abundantly expressed in the epidermis of lesional skin of atopic dermatitis (AD). Host RNase inhibitor (RI) binds to RNase 7 and blocks its ribonuclease activity. This study aimed to evaluate the impact of RNase 7–RI interactions on AD. Methods: Cultured human primary keratinocytes, with siRNA‐mediated downregulation of RNase 7 and RI, were stimulated with the synthetic RNA polyinosinic‐polycytidylic acid (poly I:C). Induction of proinflammatory mediators was analyzed by real‐time PCR and ELISA. RI expression in AD non‐lesional and lesional skin biopsies and healthy controls was analyzed by real‐time PCR and immunostaining. RI protein release in vivo on the AD skin surface was determined by western blot. Antimicrobial and ribonuclease assays were used to investigate the functional role of RI. Results: RNase 7 inhibited the RNA‐induced expression of proinflammatory mediators in keratinocytes. Accordingly, downregulation of RNase 7 in keratinocytes enhanced RNA‐mediated induction of proinflammatory mediators, whereas downregulation of RI had the opposite effect. RI was released by damaged keratinocytes and epidermis. In vivo expression and release of RI on the skin surface were enhanced in lesional AD skin. Rinsing solution from the surface of lesional AD skin blocked the ribonuclease activity of RNase 7. The anti‐Staphylococcus aureus activity of RNase 7 was abrogated by RI. Conclusions: Our data suggest a novel role of RI as a trigger factor of inflammation in AD by blocking the ribonuclease and antimicrobial activity of RNase 7, thereby enhancing RNA‐mediated inflammation and S. aureus growth. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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