P B Ernst

CSU Mentor, Long Beach, California, United States

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Publications (127)724.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Accurate and reproducible measurement of expression of pro-inflammatory cytokines in colonic biopsies from patients with ulcerative colitis (UC) is essential for proof-of-concept and mechanism-of-action studies. Few studies have rigorously established the number of biopsies required for accurate and reproducible biomarker measurements.AimTo validate methods for measuring changes in gene expression in colonic biopsy samples.Methods Twelve colonic biopsies were obtained from each of six healthy controls, six patients with inactive UC and seven patients with active UC. Mayo endoscopic scores were used as a clinical reference standard. Quantitative PCR was used to assess mRNA expression of eight known inflammatory genes. The power to detect a reduction in gene expression in active vs. inactive UC was calculated using a linear mixed effect model.ResultsmRNA analysis of colonic biopsies is a sensitive and feasible approach for measuring inflammatory gene expression in colonic biopsies. Inflammatory biomarkers correlate with Mayo endoscopic subscores for each colonic region.For most genes, three rectal biopsies from two to four patients are required to detect changes in gene expression corresponding to active vs. inactive UC to achieve a power of 80% with an alpha of 0.05.Conclusion Our data suggest that systematic measurement of inflammatory biomarkers at the mRNA level can be a valuable tool for hypothesis testing, and assessment of clinical activity and response to therapy in ulcerative colitis.
    Alimentary Pharmacology & Therapeutics 07/2014; · 4.55 Impact Factor
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    ABSTRACT: Adenosine is a purine metabolite that can mediate anti-inflammatory responses in the digestive tract through the A2A adenosine Receptor (A2AAR). Here we examined the role of this receptor in the control of inflammation in the adoptive transfer model of colitis. Infection of A2AAR(-/-) mice with Helicobacter hepaticus increased colonic inflammation scores compared to uninfected A2AAR controls. Comparison of T cell subsets in wildtype and A2AAR(-/-) mice revealed differences in markers associated with activated helper T (Th) cells and Treg. Past studies have shown that expression of A2AAR on CD45RB(HI) and CD45RB(LO) Th cells is essential for the proper regulation of colonic inflammation. Adoptive transfer of CD45RB(HI) with CD45RB(LO) from wildtype mice into RAG1(-/-)/A2AAR(-/-) mice induced severe disease within 3 weeks, although transfer of the same subsets into RAG1(-/-) mice does not induce colitis. This suggests that the presence of A2AAR on recipient cells is also important for controlling colitis. To investigate the role of A2AAR on myeloid cells, chimeric recipients were generated by giving RAG1(-/-) or RAG1(-/-)/A2AAR(-/-) bone marrow to irradiated RAG1(-/-) mice. After adoptive transfer, these recipients did not develop colitis regardless of the A2AAR expression by the donor. Together, our results suggest that the control of inflammation in vivo is dependent on A2AAR signaling through multiple cell types that collaborate in the regulation of colitis by responding to extracellular adenosine.
    American journal of physiology. Gastrointestinal and liver physiology. 05/2014;
  • Gastroenterology 05/2014; · 12.82 Impact Factor
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    ABSTRACT: After Helicobacter pylori infection in humans, gastric epithelial cells (GECs) undergo apoptosis due to stimulation by the bacteria or inflammatory cytokines. In this study, we assessed the expression and function of brain angiogenesis inhibitor 1 (BAI1) in the engulfment of apoptotic GECs using human tissue and cells. After induction of apoptosis by H. pylori or camptothecin, there was a 5-fold increase in the binding of apoptotic GECs to THP-1 cells or peripheral blood monocyte-derived macrophages as assayed by confocal microscopy or conventional and imaging flow cytometry. Binding was impaired 95% by pretreating apoptotic cells with annexin V, underscoring the requirement for phosphatidylserine recognition. The phosphatidylserine receptor BAI1 was expressed in human gastric biopsy specimens and gastric phagocytes. To confirm the role of BAI1 in apoptotic cell clearance, the functional domain of BAI1 was used as a competitive inhibitor or BAI1 expression was inhibited by small interfering RNA. Both approaches decreased binding and engulfment >40%. Exposing THP-1 cells to apoptotic cells inhibited IL-6 production from 1340 to <364 pg/ml; however, this decrease was independent of phagocytosis. We conclude that recognition of apoptotic cells by BAI1 contributes to their clearance in the human gastric mucosa and this is associated with anti-inflammatory effects.-Das, S., Sarkar, A., Ryan, K. A., Fox, S., Berger, A. H., Juncadella, I. J., Bimczok, D., Smythies, L. E., Harris, P. R., Ravichandran, K. S., Crowe, S. E., Smith, P. D., Ernst, P. B. Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells.
    The FASEB Journal 02/2014; · 5.70 Impact Factor
  • Gastroenterology 01/2014; 147(1):26–30. · 12.82 Impact Factor
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    ABSTRACT: Food-borne Salmonella spp., are a major cause of hospitalization and death. Adenosine, an important immune regulator of inflammation, limits tissue damage during infection. CD39 (nucleoside triphosphate dephosphorylase) combined with ecto-5'-nucleotidase (CD73) metabolizes ATP to adenosine. We studied the expressions of CD39 and CD73 in tissues, and T helper cells in mice after Salmonella infection and evaluated the role of CD73 in regulating immune responses and bacterial clearance in wild-type and CD73-deficient (CD73(-/-)) mice. Both CD39 and CD73 transcript levels declined in the infected wild-type mice. Compared to wild-type mice, tissues from infected CD73(-/-) mice had significantly higher expression of pro-inflammatory cytokines and reduced anti-inflammatory responses. CD73(-/-) mice were more resistant to infection and had a greater inflammatory responses and a significantly lower bacterial load in the liver compared to wild-type mice. Thus, CD73 expression attenuates inflammation during murine Salmonellosis and impairs immunity, leading to increased bacterial colonization and prolonged infection.
    Scientific Reports 01/2014; 4:4486. · 5.08 Impact Factor
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    ABSTRACT: Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR(+) mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori-induced macrophage TNF-α, which was expressed at higher levels in H. pylori-infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori-infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.
    The Journal of Immunology 05/2013; · 5.52 Impact Factor
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    ABSTRACT: The cytoplasmic Elmo1:Dock180 complex acts as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac and functions downstream of the phagocytic receptor BAI1 during apoptotic cell clearance, and in the entry of Salmonella and Shigella into cells [1-7]. We discovered an unexpected binding between Elmo1 and the Mediator complex subunit Med31. The Mediator complex is a regulatory hub for nearly all gene transcription via RNA polymerase II, bridging the general transcription machinery with gene-specific regulatory proteins [8-14]. Med31 is the smallest and the most evolutionarily conserved Mediator subunit [15, 16], and knockout of Med31 results in embryonic lethality in mice [17]; however, Med31 function in specific biological contexts is poorly understood. We observed that in primary macrophages, during Salmonella infection, Elmo1 and Med31 specifically affected expression of the cytokine genes Il10 and Il33 among the >25 genes monitored. Although endogenous Med31 is predominantly nuclear localized, Elmo1 increased the cytoplasmic localization of Med31. We identify ubiquitination as a novel posttranslational modification of Med31, with the cytoplasmic monoubiquitinated form of Med31 being enhanced by Elmo1. These data identify Elmo1 as a novel regulator of Med31, revealing a previously unrecognized link between cytoplasmic signaling proteins and the Mediator complex.
    Current biology: CB 12/2012; · 10.99 Impact Factor
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    ABSTRACT: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract (GI) for which treatments with immunosuppressive drugs has significant side-effects. Consequently, there is an clinical need for site-specific and non-toxic delivery of therapeutic genes or drugs for CD and related disorders such as inflammatory bowel disease. The aim of this study was to validate an gene delivery platform based on ultrasound-activated lipid-shelled microbubbles (MB) targeted to inflamed mesenteric endothelium in the CD-like TNFΔARE mouse model. MB bearing luciferase plasmid were functionalized with antibodies to MAdCAM-1 (MB-M) or VCAM-1 (MB-V), biomarkers of gut endothelial cell inflammation and evaluated in an in vitro flow chamber assay with appropriate ligands to confirm targeting specificity. Following MB retro-orbital injection in TNFΔARE mice, the mean contrast intensity in the ileocecal region from accumulated MB-M and MB-V was 8.5-fold and 3.6-fold greater, respectively, compared to MB-C. Delivery of luciferase plasmid to the GI tract in TNFΔARE mice was achieved by insonating the endothelial cell-bound agents using a commercial sonoporator. Luciferease expression in the midgut was detected 48 hours laster by bioluminescence imaging and further confirmed by immunohistochemical staining. The liver, spleen, heart, and kidney had no detectable bioluminesence following insonation. Transfection of the microcirculation guided by a targeted, acoustically-activated platform such as a ultrasound contrast agent microbubble has the potential to be a minimally-invasive treatment strategy to ameliorate CD and other inflammatory conditions.
    Journal of Controlled Release 11/2012; · 7.63 Impact Factor
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    ABSTRACT: Severe Clostridium difficile toxin-induced enteritis is characterized by exuberant intestinal tissue inflammation, epithelial disruption and diarrhea. Adenosine, through its action on the adenosine A2A receptor, prevents neutrophillic adhesion and oxidative burst and inhibits inflammatory cytokine production. Alanyl-glutamine enhances intestinal mucosal repair and decreases apoptosis of enterocytes. This study investigates the protection from enteritis by combination therapy with ATL 370, an adenosine A2A receptor agonist, and alanyl-glutamine in a rabbit and murine intestinal loop models of C. difficile toxin A-induced epithelial injury. Toxin A with or without alanyl-glutamine was administered intraluminally to rabbit ileal or murine cecal loops. Animals were also given either PBS or ATL 370 parenterally. Ileal tissues were examined for secretion, histopathology, apoptosis, Cxcl1/KC and IL-10. ATL 370 decreased ileal secretion and histopathologic changes in loops treated with Toxin A. These effects were reversed by the A2A receptor antagonist, SCH 58261, in a dose-dependent manner. The combination of ATL 370 and alanyl-glutamine significantly further decreased ileal secretion, mucosal injury and apoptosis more than loops treated with either drug alone. ATL 370 and alanyl-glutamine also decreased intestinal tissue KC and IL-10. Combination therapy with an adenosine A2A receptor agonist and alanyl-glutamine is effective in reversing C. difficile toxin A-induced epithelial injury, inflammation, secretion and apoptosis in animals and has therapeutic potential for the management of C. difficile infection.
    BMC Infectious Diseases 01/2012; 12:13. · 3.03 Impact Factor
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    ABSTRACT: Salmonella enterica serovar Typhimurium, a gram-negative facultative rod-shaped bacterium causing salmonellosis and foodborne disease, is one of the most common isolated Salmonella serovars in both developed and developing nations. Several S. Typhimurium genomes have been completed and many more genome-sequencing projects are underway. Comparative genome analysis of the multiple strains leads to a better understanding of the evolution of S. Typhimurium and its pathogenesis. S. Typhimurium strain UK-1 (belongs to phage type 1) is highly virulent when orally administered to mice and chickens and efficiently colonizes lymphoid tissues of these species. These characteristics make this strain a good choice for use in vaccine development. In fact, UK-1 has been used as the parent strain for a number of nonrecombinant and recombinant vaccine strains, including several commercial vaccines for poultry. In this study, we conducted a thorough comparative genome analysis of the UK-1 strain with other S. Typhimurium strains and examined the phenotypic impact of several genomic differences. Whole genomic comparison highlights an extremely close relationship between the UK-1 strain and other S. Typhimurium strains; however, many interesting genetic and genomic variations specific to UK-1 were explored. In particular, the deletion of a UK-1-specific gene that is highly similar to the gene encoding the T3SS effector protein NleC exhibited a significant decrease in oral virulence in BALB/c mice. The complete genetic complements in UK-1, especially those elements that contribute to virulence or aid in determining the diversity within bacterial species, provide key information in evaluating the functional characterization of important genetic determinants and for development of vaccines.
    PLoS ONE 01/2012; 7(7):e40645. · 3.53 Impact Factor
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    ABSTRACT: SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4(+) T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.
    AJP Gastrointestinal and Liver Physiology 09/2011; 302(1):G105-15. · 3.65 Impact Factor
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    ABSTRACT: Adenosine is an endogenous metabolite produced during hypoxia or inflammation. Previously implicated as an anti-inflammatory mediator in CD4(+) T cell regulation, we report that adenosine acts via dendritic cell (DC) A(2B) adenosine receptor (A(2B)AR) to promote the development of Th17 cells. Mouse naive CD4(+) T cells cocultured with DCs in the presence of adenosine or the stable adenosine mimetic 5'-(N-ethylcarboximado) adenosine resulted in the differentiation of IL-17- and IL-22-secreting cells and elevation of mRNA that encode signature Th17-associated molecules, such as IL-23R and RORγt. The observed response was similar when DCs were generated from bone marrow or isolated from small intestine lamina propria. Experiments using adenosine receptor antagonists and cells from A(2B)AR(-/-) or A(2A)AR(-/-)/A(2B)AR(-/-) mice indicated that the DC A(2B)AR promoted the effect. IL-6, stimulated in a cAMP-independent manner, is an important mediator in this pathway. Hence, in addition to previously noted direct effects of adenosine receptors on regulatory T cell development and function, these data indicated that adenosine also acts indirectly to modulate CD4(+) T cell differentiation and suggested a mechanism for putative proinflammatory effects of A(2B)AR.
    The Journal of Immunology 06/2011; 186(12):6746-52. · 5.52 Impact Factor
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    ABSTRACT: Inflammatory bowel disease is a chronic inflammatory disease of the gut which manifests as ulcerative colitis or Crohn's disease. One of the most studied animal models of spontaneous Crohn's disease is the senescence-accelerated mouse (SAMP1/Yit strain) model. In SAMP1/Yit mice, although many immunological responses are perturbed, some evidence suggests that the primary defect lies in the epithelial cell barrier. In the process of studying epithelial permeability, we observed that the stomach in SAMP1/Yit mice also had increased permeability. Upon further examination, these mice were shown to have marked, chronic gastritis with focal to diffuse aggregates of mononuclear cells of mixed lineages. These aggregates were located predominantly in the oxyntic mucosa, with occasional lesions in the forestomach but with relatively fewer cellular infiltrates in the antral mucosa. Real-time RT PCR showed an increase in several helper T cell (Th cell)-derived pro-inflammatory cytokines in the gastric mucosa of SAMP1/Yit mice. However, many of the cells in the aggregates of SAMP1/Yit mice were B cells. SAMP1/Yit B cells exacerbate ileitis when co-transferred into immunodeficient recipients. The gastritis also reflects a contribution by B cells. As SAMP1/Yit mice were derived from AKR mice, we examined AKR mice and determined that they too have an increased occurrence of gastritis, although they do not develop ileitis. B cells contributed to the gastric inflammation in these mice also. Thus, SAMP1/Yit mice display gastritis as well as ileitis, and B cells appear to play a role in the pathogenesis of inflammation at both sites. This review will discuss some of the mechanisms that may account for these different manifestations of gastrointestinal disease.
    The Keio Journal of Medicine 06/2011; 60(2):65-8.
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    ABSTRACT:   Helicobacter pylori (H. pylori) is a gram negative bacterium that can cause diseases such as peptic ulcers and gastric cancer. IL-17A, a proinflammatory cytokine that can induce the production of CXC chemokines for neutrophil recruitment, has recently been shown to be elevated in both H. pylori-infected patients and mice. Furthermore, studies in mouse models of vaccination have reported levels significantly increased over infected, unimmunized mice and blocking of IL-17A during the challenge phase in immunized mice reduces protective immunity. Because many aspects of immunity had redundant or compensatory mechanisms, we investigated whether mice could be protectively immunized when IL-17A function is absent during the entire immune response using IL-17A and IL-17A receptor knockout (KO) mice immunized against H. pylori.   Gastric biopsies were harvested from naïve, unimmunized/challenged, and immunized/challenged wild type (WT) and KO mice and analyzed for inflammation, neutrophil, and bacterial levels. Groups of IL-17A KO mice were also treated with anti-IFNγ or control antibodies.   Surprisingly, all groups of immunized KO mice reduced their bacterial loads comparably to WT mice. The gastric neutrophil counts did not vary significantly between IL-17A KO and WT mice, whereas IL-17RA KO mice had on average a four-fold decrease compared to WT. Additionally, we performed an immunization study with CXCR2 KO mice and observed significant gastric neutrophils and reduction in bacterial load.   These data suggest that there are compensatory mechanisms for protection against H. pylori and for neutrophil recruitment in the absence of an IL-17A-CXC chemokine pathway.
    Helicobacter 06/2011; 16(3):169-78. · 3.51 Impact Factor
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    ABSTRACT: The Salmonella enterica serovar Typhimurium strain UK-1 exhibits the highest invasion and virulence attributes among the most frequently studied strains. S. Typhimurium UK-1 has been used as the foundation for developing recombinant vaccines and has been used extensively on virulence and colonization studies in chickens and mice. We describe here the complete genome sequence of S. Typhimurium UK-1. Comparative genomics of Salmonella Typhimurium will provide insight into factors that determine virulence and invasion.
    Journal of bacteriology 05/2011; 193(15):4035-6. · 3.94 Impact Factor
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    ABSTRACT: Adenosine accumulates in inflammation and ischemia but it is more than an end-product of ATP catabolism. Signaling through different receptors with distinct, cell-specific cytoplasmic pathways, adenosine is now recognized as an inducible switch that regulates the immune system. By acting through the A(2A)AR, adenosine shapes T cell function, largely by conferring an anti-inflammatory tone on effector Th cells (Teff) and natural killer (NK)T cells. In contrast, both the A(2A)AR and A(2B)AR are expressed by antigen-presenting cells (APC) which have been shown to regulate innate responses and the transition to adaptive immunity. There is also emerging evidence that adenosine production is one mechanism that allows some pathogens as well as neoplasms to evade host defenses. This review discusses the immunoregulatory functions of adenosine and some of the interactions it may have in regulating host-microbial interactions.
    Immunologic Research 05/2011; 50(1):69-77. · 3.53 Impact Factor
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    ABSTRACT: Bacterial recognition by host cells is essential for initiation of infection and the host response. Bacteria interact with host cells via multiple pattern recognition receptors that recognize microbial products or pathogen-associated molecular patterns. In response to this interaction, host cell signaling cascades are activated that lead to inflammatory responses and/or phagocytic clearance of attached bacteria. Brain angiogenesis inhibitor 1 (BAI1) is a receptor that recognizes apoptotic cells through its conserved type I thrombospondin repeats and triggers their engulfment through an ELMO1/Dock/Rac1 signaling module. Because thrombospondin repeats in other proteins have been shown to bind bacterial surface components, we hypothesized that BAI1 may also mediate the recognition and clearance of pathogenic bacteria. We found that preincubation of bacteria with recombinant soluble BAI1 ectodomain or knockdown of endogenous BAI1 in primary macrophages significantly reduced binding and internalization of the Gram-negative pathogen Salmonella typhimurium. Conversely, overexpression of BAI1 enhanced attachment and engulfment of Salmonella in macrophages and in heterologous nonphagocytic cells. Bacterial uptake is triggered by the BAI1-mediated activation of Rac through an ELMO/Dock-dependent mechanism, and inhibition of the BAI1/ELMO1 interaction prevents both Rac activation and bacterial uptake. Moreover, inhibition of ELMO1 or Rac function significantly impairs the proinflammatory response to infection. Finally, we show that BAI1 interacts with a variety of Gram-negative, but not Gram-positive, bacteria through recognition of their surface lipopolysaccharide. Together these findings identify BAI1 as a pattern recognition receptor that mediates nonopsonic phagocytosis of Gram-negative bacteria by macrophages and directly affects the host response to infection.
    Proceedings of the National Academy of Sciences 02/2011; 108(5):2136-41. · 9.81 Impact Factor
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    Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
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    ABSTRACT: Hypoxia-inducible factor 1 (HIF1) consists of a hypoxia-inducible α subunit and a constitutively expressed β subunit. Reactive oxygen species (ROS) induced by Helicobacter pylori stabilize HIF1α in the human gastric epithelium in normoxia. HIF1α plays crucial role in carcinogenesis and has been associated with malignant progression of gastric cancer. Several genes contain functional hypoxia-response elements (HREs) in their promoters including Bcl2 family member, Mcl1. Cellular ratios of antiapoptotic oncogenic protein, Mcl1, and tumor suppressor proapoptotic protein, Noxa, determine cell fate by regulating normal cellular growth, cell death and oncogenic processes. The aim of the present study was to examine the mechanism of HIF1α induction in the H. pylori-infected gastric epithelium to better understand disease pathogenesis by H. pylori relevant to gastric carcinogenesis. Our data showed that the dose-dependent increase in HIF1α in H. pylori-infected gastric epithelia is mediated by induction of a ROS-inducible protein, apurinic/apyrimidinic endonuclease 1 (APE1), and an enhanced interaction of APE1 with the transcriptional coactivator p300. Surprisingly, with accumulation of HIF1α, further transcriptional activation of mcl1 was not observed. We identified a HIF-binding site (HBS) in the hif1α promoter and showed that increased HIF1α expression, whether H. pylori-induced or hypoxia-mimetic agent, CoCl(2)-induced, resulted in enhanced HIF1α binding to its own promoter. This resulted in a transcriptionally inactive hif1α promoter since hif1α HBS lacks HIF ancillary sequence (HAS) required for HIF1 transcriptional activity. We conclude that enhanced binding of "nonfunctional" HIF1α to hif1α promoter and limiting availability of p300 in the cell serves as checkpoints for uncontrolled HIF1α activity.
    AJP Gastrointestinal and Liver Physiology 11/2010; 299(5):G1177-86. · 3.65 Impact Factor

Publication Stats

4k Citations
724.24 Total Impact Points

Institutions

  • 2014
    • CSU Mentor
      Long Beach, California, United States
  • 2012–2014
    • University of California, San Diego
      • Department of Pathology
      San Diego, California, United States
  • 1970–2010
    • University of Virginia
      • • Division of Gastroenterology and Hepatology
      • • Department of Medicine
      • • Division of Maternal Fetal Medicine
      Charlottesville, VA, United States
  • 1994–2008
    • University of Texas Medical Branch at Galveston
      • • Department of Pediatrics
      • • Department of Internal Medicine
      • • Department of Microbiology and Immunology
      • • School of Medicine
      Galveston, TX, United States
  • 2001
    • American University Washington D.C.
      Washington, Washington, D.C., United States
  • 1998
    • Queen's University Belfast
      Béal Feirste, N Ireland, United Kingdom
  • 1985–1996
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada