Betulinic Acid Potentiates Mast Cell Degranulation by Compromising Cell Membrane Integrity and Without Involving Fcεri Receptors

ABSTRACT

Mast cells play important role in acquired and natural immunity making these favorable therapeutic targets in various inflammatory diseases. Here we observed that, pentacyclic tri terpenoid betulinic acid (BA) treatment resulted in a significantly high number (9%) of cells positive for Hoechst and negative for annexin-V indicating that BA could interfere with plasma membrane integrity. The degranulation of both activated and non-activated mast cells was enhanced upon treatment with BA. The pre-treatment of BA had remarkable effect on calcium response in activated mast cells which showed increased calcium influx relative compared to untreated cells. The results also showed potentially less migration of BA treated mast cells signifying the possible effect of BA on cell membrane. BA treatment resulted in a significant increase in mRNA levels of IL-13 while as mRNA levels of other target cytokines, IL-6 and TNF-α seem to be not affected. Moreover, there was global Increase in phosphorylation of signaling proteins and no significant change in phosphorylation of FcεRI receptors indicating that the effect of BA was independent of signaling cascade or FcεRI receptor mediated mast cell aggregation. Overall, these results portray BA potentiates mast cell effector functions by compromising the membrane integrity and independent of FcεRI involvement.

KEYWORDS:

• Allergy
• betulinic acid
• exocytosis
• inflammation
• mast cells

Acknowledgments

Authors would like to thank Dr. Petr Draber and Dr. Luba Draberova of Signal transduction lab, Institute of Molecular Genetics, Academy Of Science of Czech Republic for their continuous cooperation during production of this data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

MSK acknowledges the generous support from the Research Supporting Project (RSP2024R352) by the King Saud University, Riyadh, Kingdom of Saudi Arabia.