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

Journal Article

2024

Published in: https://pubmed.ncbi.nlm.nih.gov/38504489/

Mast cells play important role in acquired and natural immunity making

these favorable therapeutic targets in various inflammatory dis-

eases. Here we observed that, pentacyclic tri terpenoid betulinic acid 10

(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 15

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 20

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, 25

these results portray BA potentiates mast cell effector functions by

compromising the membrane integrity and independent of FcεRI

involvement.