Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 11 to 20 of 116

Publication Record


Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development.
Fung CM, White JR, Brown AS, Gong H, Weitkamp JH, Frey MR, McElroy SJ
(2016) PLoS One 11: e0146542
MeSH Terms: Animals, Apoptosis, Birth Weight, Cell Proliferation, Female, Fetal Growth Retardation, Gene Expression, Goblet Cells, Humans, Ileum, Infant, Newborn, Mice, Inbred C57BL, Organ Size, Paneth Cells, Pregnancy
Show Abstract · Added April 11, 2016
Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A2-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent "first hit", rendering IUGR intestine susceptible to further injury, infection, or inflammation.
0 Communities
1 Members
0 Resources
15 MeSH Terms
mTOR disruption causes intestinal epithelial cell defects and intestinal atrophy postinjury in mice.
Sampson LL, Davis AK, Grogg MW, Zheng Y
(2016) FASEB J 30: 1263-75
MeSH Terms: Animals, Atrophy, Cell Differentiation, Cell Proliferation, Enterocytes, Enteroendocrine Cells, Epithelial Cells, Goblet Cells, Homeostasis, Intestinal Mucosa, Intestine, Small, Male, Mice, Mice, Inbred C57BL, Paneth Cells, Regeneration, Signal Transduction, Stem Cells, TOR Serine-Threonine Kinases
Show Abstract · Added March 19, 2017
Intestinal stem cells (ISCs) drive small intestinal epithelial homeostasis and regeneration. Mechanistic target of rapamycin (mTOR) regulates stem and progenitor cell metabolism and is frequently dysregulated in human disease, but its physiologic functions in the mammalian small intestinal epithelium remain poorly defined. We disrupted the genes mTOR, Rptor, Rictor, or both Rptor and Rictor in mouse ISCs, progenitors, and differentiated intestinal epithelial cells (IECs) using Villin-Cre. Mutant tissues and wild-type or heterozygous littermate controls were analyzed by histologic immunostaining, immunoblots, and proliferation assays. A total of 10 Gy irradiation was used to injure the intestinal epithelium and induce subsequent crypt regeneration. We report that mTOR supports absorptive enterocytes and secretory Paneth and goblet cell function while negatively regulating chromogranin A-positive enteroendocrine cell number. Through additional Rptor, Rictor, and Rptor/Rictor mutant mouse models, we identify mechanistic target of rapamycin complex 1 as the major IEC regulatory pathway, but mechanistic target of rapamycin complex 2 also contributes to ileal villus maintenance and goblet cell size. Homeostatic adult small intestinal crypt cell proliferation, survival, and canonical wingless-int (WNT) activity are not mTOR dependent, but Olfm4(+) ISC/progenitor population maintenance and crypt regeneration postinjury require mTOR. Overall, we conclude that mTOR regulates multiple IEC lineages and promotes stem and progenitor cell activity during intestinal epithelium repair postinjury.
0 Communities
1 Members
0 Resources
19 MeSH Terms
LMO2 Oncoprotein Stability in T-Cell Leukemia Requires Direct LDB1 Binding.
Layer JH, Alford CE, McDonald WH, Davé UP
(2016) Mol Cell Biol 36: 488-506
MeSH Terms: Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Amino Acid Substitution, Cell Line, DNA-Binding Proteins, Humans, Jurkat Cells, LIM Domain Proteins, Leukemia, T-Cell, Molecular Sequence Data, Mutation, Protein Interaction Domains and Motifs, Protein Interaction Maps, Protein Stability, Proto-Oncogene Proteins, Transcription Factors, Transcriptional Activation
Show Abstract · Added January 26, 2016
LMO2 is a component of multisubunit DNA-binding transcription factor complexes that regulate gene expression in hematopoietic stem and progenitor cell development. Enforced expression of LMO2 causes leukemia by inducing hematopoietic stem cell-like features in T-cell progenitor cells, but the biochemical mechanisms of LMO2 function have not been fully elucidated. In this study, we systematically dissected the LMO2/LDB1-binding interface to investigate the role of this interaction in T-cell leukemia. Alanine scanning mutagenesis of the LIM interaction domain of LDB1 revealed a discrete motif, R(320)LITR, required for LMO2 binding. Most strikingly, coexpression of full-length, wild-type LDB1 increased LMO2 steady-state abundance, whereas coexpression of mutant proteins deficient in LMO2 binding compromised LMO2 stability. These mutant LDB1 proteins also exerted dominant negative effects on growth and transcription in diverse leukemic cell lines. Mass spectrometric analysis of LDB1 binding partners in leukemic lines supports the notion that LMO2/LDB1 function in leukemia occurs in the context of multisubunit complexes, which also protect the LMO2 oncoprotein from degradation. Collectively, these data suggest that the assembly of LMO2 into complexes, via direct LDB1 interaction, is a potential molecular target that could be exploited in LMO2-driven leukemias resistant to existing chemotherapy regimens.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
0 Communities
2 Members
0 Resources
17 MeSH Terms
Immunomodulatory metabolites released by the frog-killing fungus Batrachochytrium dendrobatidis.
Rollins-Smith LA, Fites JS, Reinert LK, Shiakolas AR, Umile TP, Minbiole KP
(2015) Infect Immun 83: 4565-70
MeSH Terms: Adenosine, Animals, Apoptosis, Cell Survival, Chytridiomycota, Drug Synergism, Host-Pathogen Interactions, Humans, Jurkat Cells, Kynurenine, Lymphocytes, Mycoses, Skin, Thionucleosides, Tryptophan, Xenopus laevis
Show Abstract · Added April 18, 2017
Batrachochytrium dendrobatidis is a fungal pathogen in the phylum Chytridiomycota that causes the skin disease chytridiomycosis. Chytridiomycosis is considered an emerging infectious disease linked to worldwide amphibian declines and extinctions. Although amphibians have well-developed immune defenses, clearance of this pathogen from the skin is often impaired. Previously, we showed that the adaptive immune system is involved in the control of the pathogen, but B. dendrobatidis releases factors that inhibit in vitro and in vivo lymphocyte responses and induce lymphocyte apoptosis. Little is known about the nature of the inhibitory factors released by this fungus. Here, we describe the isolation and characterization of three fungal metabolites produced by B. dendrobatidis but not by the closely related nonpathogenic chytrid Homolaphlyctis polyrhiza. These metabolites are methylthioadenosine (MTA), tryptophan, and an oxidized product of tryptophan, kynurenine (Kyn). Independently, both MTA and Kyn inhibit the survival and proliferation of amphibian lymphocytes and the Jurkat human T cell leukemia cell line. However, working together, they become effective at much lower concentrations. We hypothesize that B. dendrobatidis can adapt its metabolism to release products that alter the local environment in the skin to inhibit immunity and enhance the survival of the pathogen.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
0 Communities
1 Members
0 Resources
16 MeSH Terms
IL-33 Signaling Protects from Murine Oxazolone Colitis by Supporting Intestinal Epithelial Function.
Waddell A, Vallance JE, Moore PD, Hummel AT, Wu D, Shanmukhappa SK, Fei L, Washington MK, Minar P, Coburn LA, Nakae S, Wilson KT, Denson LA, Hogan SP, Rosen MJ
(2015) Inflamm Bowel Dis 21: 2737-46
MeSH Terms: Adult, Animals, Child, Colitis, Colitis, Ulcerative, Colon, Cytokines, Goblet Cells, Humans, Immunohistochemistry, Interleukin-1 Receptor-Like 1 Protein, Interleukin-33, Intestinal Mucosa, Intestines, Mice, Oxazolone, Real-Time Polymerase Chain Reaction, Receptors, Interleukin, Signal Transduction, Up-Regulation
Show Abstract · Added September 28, 2015
BACKGROUND - IL-33, a member of the IL-1 cytokine family that signals through ST2, is upregulated in ulcerative colitis (UC); however, the role of IL-33 in colitis remains unclear. IL-33 augments type 2 immune responses, which have been implicated in UC pathogenesis. We sought to determine the role of IL-33 signaling in oxazolone (OXA) colitis, a type 2 cytokine-mediated murine model of UC.
METHODS - Colon mucosal IL-33 expression was compared between pediatric and adult UC and non-IBD patients using immunohistochemistry and real-time PCR. OXA colitis was induced in WT, IL-33, and ST2 mice, and histopathology, cytokine levels, and goblet cells were assessed. Transepithelial resistance was measured across IL-33-treated T84 cell monolayers.
RESULTS - Colon mucosal IL-33 was increased in pediatric patients with active UC and in OXA colitis. IL-33 and ST2 OXA mice exhibited increased disease severity compared with WT OXA mice. OXA induced a mixed mucosal cytokine response, but few differences were observed between OXA WT and IL-33 or ST2 mice. Goblet cells were significantly decreased in IL-33 and ST2 OXA compared with WT OXA mice. IL-33 augmented transepithelial resistance in T84 cells, and this effect was blocked by the ERK1/2 inhibitor PD98,059.
CONCLUSIONS - OXA colitis is exacerbated in IL-33 and ST2 mice. Increased mucosal IL-33 in human UC and murine colitis may be a homeostatic response to limit inflammation, potentially through effects on epithelial barrier function. Further investigation of IL-33 protective mechanisms would inform the development of novel therapeutic approaches.
0 Communities
3 Members
0 Resources
20 MeSH Terms
Bombesin Preserves Goblet Cell Resistin-Like Molecule β During Parenteral Nutrition but Not Other Goblet Cell Products.
Busch RA, Heneghan AF, Pierre JF, Neuman JC, Reimer CA, Wang X, Kimple ME, Kudsk KA
(2016) JPEN J Parenter Enteral Nutr 40: 1042-9
MeSH Terms: Animals, Bombesin, Goblet Cells, Hormones, Ectopic, Ileum, Immunity, Innate, Interleukin-13, Interleukin-4, Male, Mice, Mice, Inbred ICR, Mucin-2, Paneth Cells, Parenteral Nutrition, Trefoil Factor-3
Show Abstract · Added August 2, 2016
INTRODUCTION - Parenteral nutrition (PN) increases the risk of infection in critically ill patients and is associated with defects in gastrointestinal innate immunity. Goblet cells produce mucosal defense compounds, including mucin (principally MUC2), trefoil factor 3 (TFF3), and resistin-like molecule β (RELMβ). Bombesin (BBS), a gastrin-releasing peptide analogue, experimentally reverses PN-induced defects in Paneth cell innate immunity. We hypothesized that PN reduces goblet cell product expression and PN+BBS would reverse these PN-induced defects.
METHODS - Two days after intravenous cannulation, male Institute of Cancer Research mice were randomized to chow (n = 15), PN (n = 13), or PN+BBS (15 µg tid) (n = 12) diets for 5 days. Defined segments of ileum and luminal fluid were analyzed for MUC2, TFF3, and RELMβ by quantitative reverse transcriptase polymerase chain reaction and Western blot. Th2 cytokines interleukin (IL)-4 and IL-13 were measured by enzyme-linked immunosorbent assay.
RESULTS - Compared with chow, PN significantly reduced MUC2 in ileum (P < .01) and luminal fluid (P = .01). BBS supplementation did not improve ileal or luminal MUC2 compared with PN (P > .3). Compared with chow, PN significantly reduced TFF3 in ileum (P < .02) and luminal fluid (P < .01). BBS addition did not improve ileal or luminal TFF3 compared with PN (P > .3). Compared with chow, PN significantly reduced ileal RELMβ (P < .01). BBS supplementation significantly increased ileal RELMβ to levels similar to chow (P < .03 vs PN; P > .6 vs chow). Th2 cytokines were decreased with PN and returned to chow levels with BBS.
CONCLUSION - PN significantly impairs the goblet cell component of innate mucosal immunity. BBS only preserves goblet cell RELMβ during PN but not other goblet cell products measured.
© 2015 American Society for Parenteral and Enteral Nutrition.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Transcriptional corepressor MTG16 regulates small intestinal crypt proliferation and crypt regeneration after radiation-induced injury.
Poindexter SV, Reddy VK, Mittal MK, Williams AM, Washington MK, Harris E, Mah A, Hiebert SW, Singh K, Chaturvedi R, Wilson KT, Lund PK, Williams CS
(2015) Am J Physiol Gastrointest Liver Physiol 308: G562-71
MeSH Terms: Animals, Apoptosis, Cell Proliferation, Cell Survival, DNA Damage, Female, Gamma Rays, Gene Expression Regulation, Goblet Cells, Histones, Intestinal Mucosa, Intestine, Small, Male, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins, Phenotype, Radiation Injuries, Experimental, Radiation Tolerance, Regeneration, Signal Transduction, Stem Cells, Tissue Culture Techniques, Transcription Factors, Wnt3A Protein
Show Abstract · Added January 20, 2015
Myeloid translocation genes (MTGs) are transcriptional corepressors implicated in development, malignancy, differentiation, and stem cell function. While MTG16 loss renders mice sensitive to chemical colitis, the role of MTG16 in the small intestine is unknown. Histological examination revealed that Mtg16(-/-) mice have increased enterocyte proliferation and goblet cell deficiency. After exposure to radiation, Mtg16(-/-) mice exhibited increased crypt viability and decreased apoptosis compared with wild-type (WT) mice. Flow cytometric and immunofluorescence analysis of intestinal epithelial cells for phospho-histone H2A.X also indicated decreased DNA damage and apoptosis in Mtg16(-/-) intestines. To determine if Mtg16 deletion affected epithelial cells in a cell-autonomous fashion, intestinal crypts were isolated from Mtg16(-/-) mice. Mtg16(-/-) and WT intestinal crypts showed similar enterosphere forming efficiencies when cultured in the presence of EGF, Noggin, and R-spondin. However, when Mtg16(-/-) crypts were cultured in the presence of Wnt3a, they demonstrated higher enterosphere forming efficiencies and delayed progression to mature enteroids. Mtg16(-/-) intestinal crypts isolated from irradiated mice exhibited increased survival compared with WT intestinal crypts. Interestingly, Mtg16 expression was reduced in a stem cell-enriched population at the time of crypt regeneration. This is consistent with MTG16 negatively regulating regeneration in vivo. Taken together, our data demonstrate that MTG16 loss promotes radioresistance and impacts intestinal stem cell function, possibly due to shifting cellular response away from DNA damage-induced apoptosis and towards DNA repair after injury.
1 Communities
5 Members
0 Resources
25 MeSH Terms
Methotrexate-mediated inhibition of nuclear factor κB activation by distinct pathways in T cells and fibroblast-like synoviocytes.
Spurlock CF, Gass HM, Bryant CJ, Wells BC, Olsen NJ, Aune TM
(2015) Rheumatology (Oxford) 54: 178-87
MeSH Terms: Adult, Aged, Apoptosis, Arthritis, Rheumatoid, Biopterin, Case-Control Studies, Cell Line, Female, Fibroblasts, Humans, Jurkat Cells, MAP Kinase Kinase 4, Male, Methotrexate, Middle Aged, NF-kappa B, Reactive Oxygen Species, Signal Transduction, Synovial Membrane
Show Abstract · Added January 21, 2015
OBJECTIVES - Nuclear factor κB (NF-κB) is a critical activator of inflammatory processes and MTX is one of the most commonly prescribed DMARDs for treatment of RA. We sought to determine whether MTX inhibited NF-κB activity in RA and in lymphocytes and fibroblast-like synoviocytes (FLSs) and to define underlying mechanisms of action.
METHODS - An NF-κB luciferase reporter plasmid was used to measure NF-κB activation across experimental stimuli. Flow cytometry was used to quantify changes in intracellular protein levels, measure levels of reactive oxygen species and determine apoptosis. Quantitative RT-PCR was used to identify changes in MTX target genes.
RESULTS - In T cell lines, MTX (0.1 μM) inhibited activation of NF-κB via depletion of tetrahydrobiopterin (BH4) and increased Jun-N-terminal kinase (JNK)-dependent p53 activity. Inhibitors of BH4 activity or synthesis also inhibited NF-κB activation and, similar to MTX, increased JNK, p53, p21 and JUN activity. Patients with RA expressed increased levels of phosphorylated or active RelA (p65) compared with controls. Levels of phosphorylated RelA were reduced in patients receiving low-dose MTX therapy. In contrast, inhibition of NF-κB activation by MTX was not mediated via BH4 depletion and JNK activation in FLSs, but rather was completely prevented by adenosine receptor antagonists.
CONCLUSION - Our findings support a model whereby distinct pathways are activated by MTX in T cells and FLSs to inhibit NF-κB activation.
© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
0 Communities
1 Members
0 Resources
19 MeSH Terms
Molecular imaging of human tumor cells that naturally overexpress type 2 cannabinoid receptors using a quinolone-based near-infrared fluorescent probe.
Wu Z, Shao P, Zhang S, Ling X, Bai M
(2014) J Biomed Opt 19: 76016
MeSH Terms: Biomarkers, Tumor, Fluorescent Dyes, Humans, Jurkat Cells, Molecular Imaging, Molecular Probes, Quinolones, Receptor, Cannabinoid, CB2
Show Abstract · Added April 2, 2019
Cannabinoid CB2 receptors (CB2R) hold promise as therapeutic targets for treating diverse diseases, such as cancers, neurodegenerative diseases, pain, inflammation, osteoporosis, psychiatric disorders, addiction, and immune disorders. However, the fundamental role of CB2R in the regulation of diseases remains unclear, largely due to a lack of reliable imaging tools for the receptors. The goal of this study was to develop a CB2R-targeted molecular imaging probe and evaluate the specificity of the probe using human tumor cells that naturally overexpress CB2R. To synthesize the CB2R-targeted probe (NIR760-Q), a conjugable CB2R ligand based on the quinolone structure was first prepared, followed by bioconjugation with a near-infrared (NIR) fluorescent dye, NIR760. In vitro fluorescence imaging and competitive binding studies showed higher uptake of NIR760-Q than free NIR760 dye in Jurkat human acute T-lymphoblastic leukemia cells. In addition, the high uptake of NIR760-Q was significantly inhibited by the blocking agent, 4-quinolone-3-carboxamide, indicating specific binding of NIR760-Q to the target receptors. These results indicate that the NIR760-Q has potential in diagnostic imaging of CB2R positive cancers and elucidating the role of CB2R in the regulation of disease progression.
0 Communities
1 Members
0 Resources
MeSH Terms
The microfluidic multitrap nanophysiometer for hematologic cancer cell characterization reveals temporal sensitivity of the calcein-AM efflux assay.
Byrd TF, Hoang LT, Kim EG, Pfister ME, Werner EM, Arndt SE, Chamberlain JW, Hughey JJ, Nguyen BA, Schneibel EJ, Wertz LL, Whitfield JS, Wikswo JP, Seale KT
(2014) Sci Rep 4: 5117
MeSH Terms: Animals, Calcium-Binding Proteins, Cell Separation, Equipment Design, Equipment Failure Analysis, Flow Cytometry, Fluoresceins, Humans, Jurkat Cells, Leukemia, T-Cell, Microfluidic Analytical Techniques, Nanotechnology, Optical Tweezers, Reproducibility of Results, Sensitivity and Specificity, Tissue Array Analysis
Show Abstract · Added February 2, 2015
Cytometric studies utilizing flow cytometry or multi-well culture plate fluorometry are often limited by a deficit in temporal resolution and a lack of single cell consideration. Unfortunately, many cellular processes, including signaling, motility, and molecular transport, occur transiently over relatively short periods of time and at different magnitudes between cells. Here we demonstrate the multitrap nanophysiometer (MTNP), a low-volume microfluidic platform housing an array of cell traps, as an effective tool that can be used to study individual unattached cells over time with precise control over the intercellular microenvironment. We show how the MTNP platform can be used for hematologic cancer cell characterization by measuring single T cell levels of CRAC channel modulation, non-translational motility, and ABC-transporter inhibition via a calcein-AM efflux assay. The transporter data indicate that Jurkat T cells exposed to indomethacin continue to accumulate fluorescent calcein for over 60 minutes after calcein-AM is removed from the extracellular space.
1 Communities
2 Members
0 Resources
16 MeSH Terms