Publikationsdatenbank

Interaction of reactive oxygen species and the JAK/STAT pathway in the sensory perception of itch (2021)

Art

Poster

Autoren

Wilzopolski, J. (WE 14)

Canbolat, P. M. (WE 14)

Bäumer, W. (WE 14)

Kongress

87th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) With contribution of the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e. V. (AGAH)

01.03. – 03.04.2021

Quelle

Naunyn-Schmiedeberg's archives of pharmacology

Bandzählung: 394

Heftzählung: Supplement 1

Seiten: S27

ISSN: 0028-1298

Verweise

URL (Volltext): https://link.springer.com/article/10.1007/s00210-021-02066-6

DOI: 10.1007/s00210-021-02066-6

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Question:
Reactive oxygen species (ROS) are involved in physiological andpathophysiological processes in mammals. They are constantly produced as secondmessengers in keratinocytes as a reaction to exogenous and endogenous stimuli. A roleof oxidative stress is discussed in the context of atopic dermatitis (AD) and itch, asintradermal injection of the naturally occurring ROS H2O2 into the neck of mice leads to arobust scratching response. The role of the Janus kinase/Signal Transducers andActivators of Transcription (JAK/STAT) pathway in AD and itch has recently gainedparticular attention and two JAK-inhibitors are approved for its therapy in human andveterinary medicine, respectively. Various studies show that ROS modulate the activity ofJAK/STAT. The exact mechanisms in itch perception and AD mediated through ROS inassociation with JAK/STAT are not clear yet. Various studies indicate an increase or adecrease in JAK activity depending on the cell type, stimuli and study conditions.According to literature a possible intersection seems to be the modulation of JAK2 throughH2O2. Therefore, the aim of this study is to investigate the role of JAK/STAT in thesignalling of ROS induced sensory perception.

Methods:
Primary small diameter mouse dorsal root ganglion (DRG) neurons areexposed to H2O2 and subtype selective JAK inhibitors of different profile and theiractivation is measured via real-time fluorescence Ca2+ imaging.

Results:
Murine DRG neurons are activated by H2O2 (7.2 %). This signal is not alteredby the preferentially selective JAK3-inhibitor tofacitinib (7.8 %). In combination with therelatively selective JAK1-inhibitor oclacitinib approximately twice as many neurons reactedto H2O2 (14.2 %). The signal is reduced in combination of H2O2 with the relativelyselective JAK2-inhibitor BMS911543 (3.0 %) or the JAK1/2-inhibitor AZD1480 (3.6 %).

Conclusion:
The above-mentioned results indicate an involvement of JAK1 and JAK2 inH2O2 activation of sensory neurons