Profiles of Lamina Propria T Helper Cell Subsets Discriminate Between Ulcerative Colitis and Crohn's Disease.
Inflammatory Bowel Diseases 22(8):1779 (2016)
Distinction between 2 forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), can be challenging. Aberrant mucosal immunity suggests that CD is a T helper type 1 cell (Th1)-driven disease, whereas UC as Th2-driven response. However, whether this paradigm trul...
Novel CD8+ T-Cell Subsets Demonstrating Plasticity in Patients with Inflammatory Bowel Disease.
Inflammatory Bowel Diseases 22(7):1596 (2016)
Distinct CD8+ T-cell subsets such as interleukin-17-expressing Tc17 and Foxp3-expressing Tcreg are functionally similar to CD4+ T cells. Though CD4+ T cells are dysregulated in patients with inflammatory bowel disease (IBD), CD8+ T cells are not well investigated. Vitamin D is an environmental f...
Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses.
Cell 162(6):1309 (2015)
Encounters between immune cells and invading bacteria ultimately determine the course of infection. These interactions are usually measured in populations of cells, masking cell-to-cell variation that may be important for infection outcome. To characterize the gene expression variation that unde...
Integrated Genomics of Crohn's Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy.
Cell Reports 11(12):1905 (2015)
The polymorphism ATG16L1 T300A, associated with increased risk of Crohn's disease, impairs pathogen defense mechanisms including selective autophagy, but specific pathway interactions altered by the risk allele remain unknown. Here, we use perturbational profiling of human peripheral blood cells...
An image-based genetic assay identifies genes in T1D susceptibility loci controlling cellular antiviral immunity in mouse.
PLoS ONE 9(9):e108777 (2014)
The pathogenesis of complex diseases, such as type 1 diabetes (T1D), derives from interactions between host genetics and environmental factors. Previous studies have suggested that viral infection plays a significant role in initiation of T1D in genetically predisposed individuals. T1D susceptib...
Atg16l1 is required for autophagy in intestinal epithelial cells and protection of mice from Salmonella infection.
Gastroenterology 145(6):1347 (2013)
Intestinal epithelial cells aid in mucosal defense by providing a physical barrier against entry of pathogenic bacteria and secreting antimicrobial peptides (AMPs). Autophagy is an important component of immune homeostasis. However, little is known about its role in specific cell types during ba...
The EGF receptor and HER2 participate in TNF-α-dependent MAPK activation and IL-8 secretion in intestinal epithelial cells.
Mediators of Inflammation 2012:207398 (2012)
TNF-α activates multiple mitogen-activated protein kinase (MAPK) cascades in intestinal epithelial cells (IECs) leading to the secretion of interleukin 8 (IL-8), a neutrophil chemoattractant and an angiogenic factor with tumor promoting properties. As the epidermal growth factor receptor (EGFR) ...
AMP-activated protein kinase is a positive regulator of poly(ADP-ribose) polymerase.
Biochemical and Biophysical Research Communicat... 342(1):336 (2006)
AMPK acts as a cellular fuel gauge and responds to decreased cellular energy status by inhibiting ATP-consuming pathways and increasing ATP-synthesis. The aim of this study was to examine the role of AMPK in modulating poly(ADP-ribose) polymerase (PARP), a nuclear enzyme involved in maintaining ...
Adenosine is a negative regulator of NF-kappaB and MAPK signaling in human intestinal epithelial cells.
Cellular Immunology 237(2):86 (2005)
Previous studies suggest that adenosine possesses anti-inflammatory properties, however, the mechanisms by which adenosine affects immune function remain unclear, particularly in the intestine. In this study, we hypothesized that adenosine directly affects pro-inflammatory gene expression in int...
Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells.
Breast Cancer Research and Treatment 92(2):187 (2005)
The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells in animal models and cell lines, but the mechanism by which this occurs is not well understood. In order to explore possible mechanisms for the modulation of breas...
Serum amyloid A activates NF-kappaB and proinflammatory gene expression in human and murine intestinal epithelial cells.
European Journal of Immunology 35(3):718 (2005)
Serum amyloid A (SAA) is an acute-phase protein whose levels positively correlate with disease activity in inflammatory bowel diseases. In this study we investigated the impact of SAA on NF-kappaB signaling and proinflammatory gene expression in intestinal epithelial cells (IEC). Human HT-29 and...
5-aminoimidazole-4-carboxamide riboside (AICAR) enhances GLUT2-dependent jejunal glucose transport: a possible role for AMPK.
Biochemical Journal 385(Pt 2):485 (2005)
AMPK (AMP-activated protein kinase) is a key sensor of energy status within the cell. Activated by an increase in the AMP/ATP ratio, AMPK acts to limit cellular energy depletion by down-regulating selective ATP-dependent processes. The purpose of the present study was to determine the role of AM...
Activation of AMP-activated protein kinase reduces cAMP-mediated epithelial chloride secretion.
American Journal of Physiology - Gastrointestin... 285(5):G850 (2003)
AMP-activated protein kinase (AMPK) is activated in response to fluctuations in cellular energy status caused by oxidative stress. One of its targets is the cystic fibrosis transmembrane conductance regulator (CFTR), which is the predominant Cl- secretory channel in colonic tissue. The aim of th...
MAP kinases contribute to IL-8 secretion by intestinal epithelial cells via a posttranscriptional mechanism.
American Journal of Physiology - Cell Physiology 283(1):C31 (2002)
The intracellular pathways that regulate intestinal epithelial gene expression are poorly understood. In this study we examined the roles of extracellular signal-regulated kinase (ERK) and p38 in the expression of interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) using the huma...