Joseph R. Woska, Jr., St. John’s University Student
Marc E. Gillespie, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences
Abstract: Uncovering or identifying novel mast cell targets that mediate disease or disease progression may lead to the development of novel therapeutics for the treatment of allergy/asthma and autoimmune disease. Mast cells are granulocytes that emanate from myeloid progenitors in the bone marrow and play a critical role in innate immunity as vital sentinel cells that combat invading microorganisms through the release of a plethora of inflammatory mediators. However, dysregulation of mast cell function can lead to allergic disease and autoimmune disease, which affect > 80 million persons in the United States alone. The transport and fusion of inflammatory mediator-laden vesicles to the membrane in granulocytes and their subsequent exocytosis have been postulated to be mediated by a family of evolutionarily-conserved proteins known as the SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors). The expression and functional role(s) of two SNARE family members SNAP-25 and SNAP-23 in mast cell degranulation have not been fully elucidated. In this study, we aim to use RNA interference methods (siRNA oligos to SNAP-25 and SNAP-23) and gene overexpression studies (with SNAP-25 and/or SNAP-23) to fully examine the role of both proteins in Fc?RI receptor-activated or Ca2+ ionophore-activate rat RBL-2H3 mast cells. These studies may allow for the identification of novel partners or complexes that can be exploited to uncover new targets for the treatment of allergic and autoimmune diseases.