BackgroundMercury is known to be neurotoxic, but its effects on the immune system are less well known. Mast cells are involved in allergic reactions, but also in innate and acquired immunity, as well as in inflammation. Many patients with Autism Spectrum Disorders (ASD) have "allergic" symptoms; moreover, the prevalence of ASD in patients with mastocytosis, characterized by numerous hyperactive mast cells in most tissues, is 10-fold higher than the general population suggesting mast cell involvement. We, therefore, investigated the effect of mercuric chloride (HgCl2) on human mast cell activation.MethodsHuman leukemic cultured LAD2 mast cells and normal human umbilical cord blood-derived cultured mast cells (hCBMCs) were stimulated by HgCl2 (0.1-10 μM) for either 10 min for beta-hexosaminidase release or 24 hr for measuring vascular endothelial growth factor (VEGF) and IL-6 release by ELISA.ResultsHgCl2 induced a 2-fold increase in β-hexosaminidase release, and also significant VEGF release at 0.1 and 1 μM (311 ± 32 pg/106 cells and 443 ± 143 pg/106 cells, respectively) from LAD2 mast cells compared to control cells (227 ± 17 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 μM) to the proinflammatory neuropeptide substance P (SP, 0.1 μM) had synergestic action in inducing VEGF from LAD2 mast cells. HgCl2 also stimulated significant VEGF release (360 ± 100 pg/106 cells at 1 μM, n = 5, p < 0.05) from hCBMCs compared to control cells (182 ± 57 pg/106 cells), and IL-6 release (466 ± 57 pg/106 cells at 0.1 μM) compared to untreated cells (13 ± 25 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 μM) to SP (5 μM) further increased IL-6 release.ConclusionsHgCl2 stimulates VEGF and IL-6 release from human mast cells. This phenomenon could disrupt the blood-brain-barrier and permit brain inflammation. As a result, the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis.
BackgroundThe fungal pathogen Candida albicans colonizes the gastrointestinal (GI) tract of mammalian hosts as a benign commensal. However, in an immunocompromised host, the fungus is capable of causing life-threatening infection. We previously showed that the major transcription factor Efg1p is differentially expressed in GI-colonizing C. albicans cells dependent on the host immune status. To understand the mechanisms that underlie this host-dependent differential gene expression, we utilized mathematical modeling to dissect host-pathogen interactions. Specifically, we used principles of evolutionary game theory to study the mechanism that governs dynamics of EFG1 expression during C. albicans colonization.ResultsMathematical modeling predicted that down-regulation of EFG1 expression within individual fungal cells occurred at different average rates in different hosts. Rather than using relatively transient signaling pathways to adapt to a new environment, we demonstrate that C. albicans overcomes the host defense strategy by modulating the activity of diverse fungal histone modifying enzymes that control EFG1 expression.ConclusionBased on our modeling and experimental results we conclude that C. albicans cells sense the local environment of the GI tract and respond to differences by altering EFG1 expression to establish optimal survival strategies. We show that the overall process is governed via modulation of epigenetic regulators of chromatin structure.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0268-1) contains supplementary material, which is available to authorized users.
Gastro-esophageal reflux disease (GERD) is a common cause of chronic cough. However, a low-cost diagnostic tool for linking GERD and cough in a cause and effect relationship is still lacking. In the present study, an intra-esophageal cough detection probe that comprises a miniature white-light interferometric fiber optic pressure sensor is proposed. This innovative catheter provides a custom encapsulation of the pressure sensor which specifically optimizes the sensitivity to pressure responses triggered by cough events. In vitro and in vivo testing results of the initial cough detection probe are presented. Experimental results demonstrated the feasibility of using the proposed catheter for identifying cough episodes. The presented work can be integrated with commercial reflux pH/impedance probes to facilitate simultaneous 24-hour ambulatory monitoring of cough and reflux events, with the ultimate goal of quantifying the temporal correlation between the two types of events.
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