A5070008665- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Asthma and respiratory diseases
- Antimicrobial Peptides and Activities
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer, Stress, Anesthesia, and Immune Response
- Lung Cancer Research Studies
- Chemokine receptors and signaling
- Adenosine and Purinergic Signaling
- Diabetes Treatment and Management
- Allergic Rhinitis and Sensitization
- Receptor Mechanisms and Signaling
- Acute Lymphoblastic Leukemia research
- Neuroendocrine Tumor Research Advances
- Glycosylation and Glycoproteins Research
- Gut microbiota and health
- Neuroendocrine regulation and behavior
- Infant Nutrition and Health
- Chemical Synthesis and Analysis
- Histone Deacetylase Inhibitors Research
- Proteoglycans and glycosaminoglycans research
- Neonatal Respiratory Health Research
- Acute Myeloid Leukemia Research
- Inflammatory mediators and NSAID effects
- Inflammatory Biomarkers in Disease Prognosis
North Dakota State University
2014-2025
Dakota State University
2006-2025
Temple University
2022
Bipar
2004
Veterans Health Administration
2003
University of California, San Francisco
2002-2003
University of California San Francisco Medical Center
2000-2001
University of Edinburgh
2001
Virginia Commonwealth University
1995-2000
Virginia Commonwealth University Medical Center
1999
Vasoactive intestinal peptide (VIP) and its G protein-coupled receptors, VPAC(1)R VPAC(2)R, are prominent in the immune system regulate many aspects of T cell-dependent immunity. In mouse cells, is expressed constitutively, whereas VPAC(2)R induced by stimuli. VPAC(2)R-null (VPAC(2)R(-/-)) mice on a C57BL/6 background shown here to have normal basic characteristics, including serum Ig concentrations, blood levels all leukocytes, spleen number total cells (CD3(+)) bearing CD4, CD8, CD28....
Abstract Sphingosine 1-phosphate (S1P) in blood, lymph, and immune tissues stimulates regulates T cell migration through their S1P1 (endothelial differentiation gene encoded receptor-1) G protein-coupled receptors. We show now that S1P1Rs also mediate suppression of proliferation cytokine production. Uptake [3H]thymidine by mouse CD4 cells stimulated with anti-CD3 mAbs plus either anti-CD28 or IL-7 was inhibited up to 50% 10−9–10−6 M S1P. Suppression S1P required Ca2+ signaling reduced...
Impaired function of the Ikaros (IKZF1) protein is associated with development high-risk B-cell precursor acute lymphoblastic leukemia (B-ALL). The mechanisms tumor suppressor activity in are unknown. binds to upstream regulatory elements its target genes and regulates their transcription via chromatin remodeling. Here, we report that represses histone H3K4 demethylase, JARID1B (KDM5B). Transcriptional repression increased global levels trimethylation. Ikaros-mediated dependent on...
Abstract Background Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide pivotal in migraine pathophysiology and considered promising new drug target. Although intravenous PACAP triggers attacks recent phase II trial with PACAP-inhibiting antibody showed efficacy prevention, targeting the receptor PAC1 alone has been unsuccessful. The present study investigated role of three receptors (PAC1, VPAC1 VPAC2) inducing migraine-relevant hypersensitivity mice. Methods Hindpaw...
Intra-abdominal sepsis is a life-threatening complex syndrome caused by microbes in the gut microbiota invading peritoneal cavity. It one of major complications intra-abdominal surgery. To date, only supportive therapies are available. No studies have investigated progression Our group has shown that platelets play an essential role during and blocking purinergic signaling through P2Y 1 12 antagonism significantly lowered inflammatory levels improved survival murine model sepsis. Here, we...
Vasoactive intestinal peptide (VIP) and its G-protein-coupled receptors (VPAC1 VPAC2 Rs) are prominent in the immune system. In T cells, VPAC1 R is expressed constitutively whereas induced only after stimulation of cell receptor (TCR) or exposure to some cytokines. also transduce different effects VIP on cells. Constitutive expression selectively CD4+ cells (helper-inducer Th cells) transgenic (TG) C57BL/6 mice directed by lck tyrosine kinase promoter now shown evoke production more Th2-type...
Ikaros encodes a transcription factor that functions as tumor suppressor in T-cell acute lymphoblastic leukemia (T-ALL). The mechanisms through which regulates gene expression and cellular proliferation T-ALL are unknown. Re-introduction of into Ikaros-null cells resulted cessation induction differentiation. We performed dynamic, global, epigenomic, analyses to determine the activity. Our results identified novel epigenetic regulation expression: directly de novo formation depletion...
An influx of monocytes is observed in many different physiological and pathophysiological states, including bone remodeling injury. These cells appear at early stages formation repair persist throughout the later stages. In experiments described here, unstimulated normal human osteoblastic did not produce detectable levels monocyte chemotactic activity. However, interleukin-1 (IL-1)-stimulated produced a chemoattractant that similar to protein-1 (MCP-1) mRNA expression, protein production,...
Asthma is frequently caused and/or exacerbated by sensitization to fungal allergens, which are ubiquitous in many indoor and outdoor environments. Severe asthma with characterized airway hyperresponsiveness bronchial constriction response an inhaled allergen that worsened environmental exposure airborne fungi leads a disease course often very difficult treat standard therapies. As result of complex interactions among inflammatory cells, structural the intercellular matrix allergic lung,...
Abstract Vasoactive intestinal peptide and its G protein-coupled receptors, VPAC1 VPAC2, regulate critical aspects of innate adaptive immunity. T cell VPAC2Rs mediate changes in cytokine generation, which potently increase the Th2/Th1 ratio consequently shift effector responses toward allergy inflammation. To examine mechanisms VPAC2 promotion Th2 phenotype, we analyzed controls IL-4 transcription CD4 cells from cell-targeted transgenic (Tg), knockout, wild-type (WT) mice. c-maf junB mRNA,...
The Ikaros gene is alternately spliced to generate multiple zinc finger proteins involved in regulation and chromatin remodeling. Whereas murine studies have provided important information regarding the role of mouse, little known function human. We report functional analyses two largest human (hIK) isoforms, hIK-VI hIK-H, T cells. Abundant expression described isoform, restricted hematopoietic find that DNA binding affinity hIK-H differs from hIK-VI. Co-expression hIk-H with hIk-VI alters...
Vasoactive intestinal peptide (VIP) is crucial for gastrointestinal tract (GIT) health. VIP sustains GIT homeostasis through maintenance of the epithelial barrier and acts as a potent anti-inflammatory mediator that contributes to gut bacterial tolerance. Based on these biological functions by VIP, we hypothesized its deficiency would alter microbial ecology. To this end, fecal samples from male female VIP+/+, VIP+/- VIP-/- littermates (n=47) were collected 16S rRNA sequencing was conducted....
There is a growing interest for viral vector-free chimeric antigen receptor (CAR) T-cells due to its ability kill cancer cells without adverse side effects. A potential avenue manufacturing viral-vector free CAR utilize mRNA electroporation. One of the major concerns with electroporated shorter cytotoxic lifespan few days, which insufficient or not ideal therapy. To better understand this issue and develop solution, study focused on examining translation molecules, time dependent degradation...
The vasoactive intestinal peptide (VIP) signaling axis constitutes a master "communication coordinator" between cells of the nervous and immune systems. To date, VIP its two main receptors expressed in T lymphocytes, receptor (VPAC)1 VPAC2, mediate critical cellular functions regulating adaptive immunity, including arresting CD4 G(1) cell cycle, protection from apoptosis potent chemotactic recruiter to mucosa associated lymphoid compartment gastrointestinal tissues. Since discovery 1970,...
Vasoactive intestinal peptide and its G-protein-coupled receptors, VPAC-1 VPAC-2, are highly expressed in the immune system modulate diverse T cell functions. The human 5'-flanking region (1.4 kb) contains four high affinity Ikaros (IK) consensus sequences. native protein from nuclear extracts IK-1 IK-2 recombinant proteins recognized an IK binding motif promoter electrophoretic mobility shift assays by a sequence-specific mechanism, anti-IK antibodies supershifted this complex. Stable...