Microbial Metabolite Butyrate Suppresses Murine Mast Cell Activation
- Hanying Zhang1,
- Min Du2,
- Yansong Xue1,
- Qiyuan Yang2 and
- Meijun Zhu1,3
- 1School of Food Science Washington State University Pullman WA United States
- 2Dept of Animal Science Washington State University Pullman WA United States
- 3School of Food Science University of Idaho Moscow ID United States
Abstract
Background: Mast cell is known for its roles in mediating food allergy and regulating gut inflammation. Butyrate, a major short chain fatty acid produced by gut microbiota, exerts beneficial effects on intestinal homeostasis. However, its role in modulating mast cell function remain undefined. Methods: Murine mastocytoma P815 cells (P815) or murine bone marrow derived mast cells (BMMC) were treated with sodium butyrate (NaB). The proliferation, cell cycle, apoptosis, degranulation and cytokine secretion were assessed.Results: In P815 cells, NaB inhibited cell proliferation, increased acetylation of both histone 3 and α-tubulin. The growth inhibition effect of NaB is probably through reducing c-kit expression and inducing cell cycle arrest and apoptosis, which is indicated by enhanced annexin V/PI staining, caspase-3 and PARP cleavage. In BMMC, NaB treatment dramatically suppressed FcεRI dependent TNFα and IL-6 release without affecting degranulation. Furthermore, NaB enhanced histone 3 acetylation but diminished mRNA expression of
Tnf -α and
Il-6, possibly through inhibiting the transcription initiation as revealed by reduced RNA polymerase II binding to the promoters of
Tnf-α and
Il-6.Conclusions: NaB modulates murine mast cell function possibly through enhancing histone acetylation, which is of importance in developing therapeutics for diseases involving mast cells (NIH R15HD073864).