# Time-sensitive effects of quercetin on rat basophilic leukemia (RBL-2H3) cell responsiveness and intracellular signaling

## TL;DR

Quercetin initially reduces mast cell activity but may increase responsiveness over time, highlighting the need for careful use in treating inflammatory diseases.

## Contribution

The study reveals time-sensitive effects of quercetin on mast cell signaling and responsiveness.

## Key findings

- Short-term quercetin treatment reduces RBL-2H3 cell activity.
- Prolonged exposure transiently enhances IgE and non-IgE-mediated responses.
- Quercetin downregulates IgE-mediated degranulation but increases sensitivity to other secretagogues.

## Abstract

Quercetin is known for its ability to inhibit mast cell degranulation and reduce the release of inflammatory mediators. However, it has also been reported to sensitize mast cells, potentially leading to hyperresponsiveness. This necessitates careful optimization of its use in the treatment of chronic inflammatory diseases. To fully harness quercetin’s therapeutic potential, this study investigated the effects of quercetin on rat basophilic leukemia (RBL-2H3) cells responsiveness over varying durations of exposure. We employed comprehensive transcriptome analysis and subsequent functional validation of key signaling pathways. Our findings revealed that quercetin initially reduced cell activity with short-term treatment. However, with prolonged exposure, quercetin transiently enhanced both IgE cross-linkage-mediated and non-IgE-mediated responses. Specifically, prolonged quercetin treatment downregulated IgE-mediated degranulation and FcεRI expression, while potentially sensitizing RBL-2H3 cells to other non-IgE secretagogues through enhanced PKC activity. Given quercetin’s multifaceted effects on intracellular signaling pathways, it is crucial to further investigate its efficacy and potential risk of adverse effects. Future studies should focus on a deeper understanding of these mechanisms to optimize quercetin’s therapeutic applications while mitigating any possible negative outcomes.