Inhibiting Degranulation in Immune Cell Signaling Pathways

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Fadul, Naja
Kasica, Zachary
Laurence, Kyeisha
Moy, Stephanie
Murugan, Sindhu
Pamala, Chinmayi
Robinson, Morgan
Shah, Rohan
Shrestha, Mansu
Smith, Marcus
Frauwirth, Kenneth
Allergies are a pervasive issue and require novel ways of alleviating symptoms. Existing treatments are focused on symptom management and immunotherapy, but there is also potential to target the molecules involved in the downstream pathway, particularly the PLCγ enzymatic pathway. Our research aimed to identify important target molecules involved in this pathway that result in the degranulation of mast cells. We intended to inhibit these molecules in order to hinder mast cell degranulation and therefore prevent allergic symptoms. Our results were tested and measured in MC/9 (mouse mast cell) and RBL-2H3 (rat basophilic) cell lines with multiple cell degranulation assays such as the beta-hexosaminidase and tryptase assay. The results were evaluated based on the comparative effect as well as specificity of inhibitors on mast cell degranulation. We aim to find the most ideal inhibitor for the PLCγ, SK, S1P2 enzymatic pathways in the signalling cascade in order to most effectively reduce degranulation and thus reduce the allergic response.