@article{d'costa_ayyadurai_gibson_mackey_rajput_sommerville_wilson_li_kubat_kumar_et al._2019, title={Mast cell corticotropin-releasing factor subtype 2 suppresses mast cell degranulation and limits the severity of anaphylaxis and stress-induced intestinal permeability}, volume={143}, ISSN={["1097-6825"]}, DOI={10.1016/j.jaci.2018.08.053}, abstractNote={Psychological stress and heightened mast cell (MC) activation are linked with important immunologic disorders, including allergy, anaphylaxis, asthma, and functional bowel diseases, but the mechanisms remain poorly defined. We have previously demonstrated that activation of the corticotropin-releasing factor (CRF) system potentiates MC degranulation responses during IgE-mediated anaphylaxis and psychological stress through corticotropin-releasing factor receptor subtype 1 (CRF1) expressed on MCs.In this study we investigated the role of corticotropin-releasing factor receptor subtype 2 (CRF2) as a modulator of stress-induced MC degranulation and associated disease pathophysiology.In vitro MC degranulation assays were performed with bone marrow-derived mast cells (BMMCs) derived from wild-type (WT) and CRF2-deficient (CRF2-/-) mice and RBL-2H3 MCs transfected with CRF2-overexpressing plasmid or CRF2 small interfering RNA. In vivo MC responses and associated pathophysiology in IgE-mediated passive systemic anaphylaxis and acute psychological restraint stress were measured in WT, CRF2-/-, and MC-deficient KitW-sh/W-sh knock-in mice.Compared with WT mice, CRF2-/- mice exhibited greater serum histamine levels and exacerbated IgE-mediated anaphylaxis and colonic permeability. In addition, CRF2-/- mice exhibited increased serum histamine levels and colonic permeability after acute restraint stress. Experiments with BMMCs and RBL-2H3 MCs demonstrated that CRF2 expressed on MCs suppresses store-operated Ca2+ entry signaling and MC degranulation induced by diverse MC stimuli. Experiments with MC-deficient KitW-sh/W-sh mice systemically engrafted with WT and CRF2-/- BMMCs demonstrated the functional importance of MC CRF2 in modulating stress-induced pathophysiology.MC CRF2 is a negative global modulator of stimuli-induced MC degranulation and limits the severity of IgE-mediated anaphylaxis and stress-related disease pathogenesis.}, number={5}, journal={JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}, author={D'Costa, Susan and Ayyadurai, Saravanan and Gibson, Amelia J. and Mackey, Emily and Rajput, Mrigendra and Sommerville, Laura J. and Wilson, Neco and Li, Yihang and Kubat, Eric and Kumar, Ananth and et al.}, year={2019}, month={May}, pages={1865-+} }
 @article{li_stahl_2014, title={Dietary Calcium Deficiency and Excess Both Impact Bone Development and Mesenchymal Stem Cell Lineage Priming in Neonatal Piglets}, volume={144}, ISSN={["1541-6100"]}, DOI={10.3945/jn.114.194787}, abstractNote={BACKGROUND
Optimizing calcium nutrition to maximize bone accretion during growth to prevent fragility fractures later in life has spurred greater interest in calcium nutrition in neonates.


OBJECTIVE
The aim of this study was to determine the effect of dietary calcium, from deficiency through excess, on bone growth, and the in vivo and in vitro behavior of mesenchymal stem cells (MSCs) in neonatal pigs.


METHODS
Twenty-four male and female piglets (24 ± 6 h old) were fed either a calcium-deficient [Ca-D; 0.6% Ca on a dry matter (DM) basis], a calcium-adequate diet (Ca-A; 0.9% Ca on a DM basis), or a calcium-excessive diet (Ca-E; 1.3% Ca on a DM basis) for 14 d to assess the impact of dietary calcium on calcium homeostasis and on the behavior of MSCs.


RESULTS
Growth rate was not affected by the Ca-E diet, although bone ash content was 16% higher (P < 0.05) and urinary calcium excretion was 5-fold higher, when normalized to creatinine, compared with the Ca-A group at trial completion. Serum parathyroid hormone (PTH) concentrations were elevated (P < 0.05) in Ca-D piglets in comparison with other groups at both 7 and 14 d. In vivo proliferation of MSCs was 30% higher (P < 0.05) in Ca-E piglets than the other groups. MSCs from both Ca-D- and Ca-E-fed piglets had greater adipogenic potential based on increased gene expression (P < 0.05) of peroxisome proliferator-activated receptor γ (Pparg) and adipocyte fatty acid-binding protein (Ap2) than MSCs from Ca-A piglets. Interestingly, only MSCs from Ca-E-fed piglets had greater (P < 0.05) gene expression of lipoprotein lipase (Lpl) during adipocytic differentiation than those from Ca-A piglets. To assess alterations in lineage allocation and priming, the most and least osteogenic (O+ and O-, respectively) and adipogenic (A+ and A-, respectively) colonies from each MSC isolation were selected on the basis of functional staining. The O+ colonies from Ca-D piglets expressed lower (P < 0.05) levels of osteocalcin (OC) mRNA than did those from other groups, whereas the O- colonies from Ca-E piglets expressed higher (P < 0.05) levels of mRNA of Pparg, Ap2, and Lpl than did those from other groups.


CONCLUSIONS
Neonatal calcium deficiency appears to reduce the osteogenic priming of MSCs while enlarging a subpopulation of potentially adipogenic cells, and excess dietary calcium appears to allow greater multipotency of MSCs. These programming alterations of MSCs could have long-term consequences for bone health.}, number={12}, journal={JOURNAL OF NUTRITION}, author={Li, Yihang and Stahl, Chad H.}, year={2014}, month={Dec}, pages={1935–1942} }