This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines included IL-6, TNF, MCP-1, MIP-1α, IL-13, and VEGF. Lactic acid pretreatment promoted a G0/G1 cell cycle arrest. Investigation into the IL-33 signaling pathway showed lactic acid decreased TAK1 and JNK phosphorylation, while increasing phosphorylated AKT levels. Blocking JNK and TAK1 with a small molecule inhibitor mimicked the effects of lactic acid. Interestingly, lactic acid significantly increased IL-33 mediated VEGF. An in vitro angiogenesis assay confirmed that mast cells were pro-angiogenic in a lactic acid-rich environment. Taken together, these data show that lactic acid impacts mast cell function, possibly promoting a pro-angiogenic, anti-inflammatory phenotype.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-4654 |
| Date | 01 January 2014 |
| Creators | Spence, Andrew J |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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