2026-05-20T22:04:36Zhttps://keep.lib.asu.edu/oai/request

oai:keep.lib.asu.edu:node-2006962025-06-06T18:40:59Zoai_pmh:alloai_pmh:repo_items

200696 https://hdl.handle.net/2286/R.2.N.200696 http://rightsstatements.org/vocab/InC/1.0/ http://creativecommons.org/licenses/by-nc-sa/4.0 2025-05 28 pages Nawaz, Fathima Florsheim, Esther Roginski, Ana Enow, Junior Barrett, The Honors College School of Human Evolution & Social Change School of Life Sciences Environmental toxins are pervasive and dangerous to human health, yet little is known about their induced immune defenses. This gap is clinically significant, as 1 in 5 deaths worldwide in children below age five is attributed to toxin-induced diarrhea. One immune cell is particularly well-positioned as a potential sensor candidate for toxic stimuli: mast cells. Along with the secretion of inflammatory cytokines, mast cells can degranulate, releasing bioactive mediators in seconds. These mediators are associated with neuronal reflexes of expulsion, such as vomiting and diarrhea. This project aims to determine the effect of oral toxins on mast cells. To investigate mast cell activation, fully differentiated and mature murine bone marrow-derived mast cells were exposed to cholera toxin, aconitine, and sennoside A, which are toxins from Vibrio cholerae bacteria, Aconitum and Senna plants respectively. Mast cell viability was determined using flow cytometry and trypan blue staining. Degranulation was measured via beta-hexosaminidase release, and cytokine production was assessed with ELISA. None of the toxins induced significant cell death. Cholera toxin and aconitine did not induce degranulation, but sennoside A partially triggered mast cell degranulation. Further, the effect of oral toxins on allergic mast cell activation were explored by treating the cultures with cholera toxin, aconitine, or sennoside A for overnight post sensitization with IgE antibodies. Mast cells were challenged with allergens for 1h before analyses. Sennoside A prevented IgE-mediated mast cell degranulation, and both sennoside A and aconitine prevented ionomycin-mediated mast cell degranulation. Sennoside A also suppressed IgE-induced secretion of pro-inflammatory cytokines TNFα and IL-6, and expression of IL-1b. Although oral toxins did not affect mast cells upon direct stimulation, my findings suggest that chemically distinct plant metabolites may prevent allergic mast cell degranulation. This study can help delineate the pathway to exploring plant metabolites as novel therapeutics for treating allergies and hypersensitivities, which continue to rise and affect millions of Americans. Mast Cells Toxins Environment Allergy Immune Defense Immune Responses to Oral Toxins