Immunopharmacology
Joseph R. Woska, Jr., St. John’s
University Student
Marc E. Gillespie, Department of
Pharmaceutical Sciences, College of Pharmacy and Allied Health
Professions
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.