Cytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors

<p>Abstract</p> <p>Background</p> <p>Stem cell transplantation as therapy for hematological disorders is often hampered by severe graft-versus-host-disease. This may be reduced by umbilical cord blood transplantation, an effect that has been attributed to qualitative differences between neonatal and adult T cells. We compared levels of secreted proteins and cytokine mRNA induced in cord blood leukocytes (CBL) and adult blood leukocytes (ABL) by various stimuli.</p> <p>Results</p> <p>While interleukin-2 (IL-2) levels were similar in CBL and ABL, there was less induction of the Th1 cytokine interferon-γ in CBL. Production of the Th2 cytokines IL-4, IL-5, and IL-13 and the hematopoietic cytokine IL-3 was much lower in CBL versus ABL after T-cell receptor-mediated stimulation, whereas production of GM-CSF was comparable in the 2 cell types. The lower levels of Th1 and Th2 cytokines were maintained in CBL during a 4-day time-course study, while after 12 hours IL-3 and GM-CSF reached in CBL levels similar to those in ABL. For all cytokines except IFNγ, the IC₅₀values for inhibition by cyclosporin A were similar in ABL and CBL. In contrast, there was less expression and activation of transcription factors in CBL. Activation of NF-κB by TPA/ionomycin was detected in ABL but not CBL. Furthermore, there was less expression of the Th subset-specific transcription factors T-bet and c-maf in CBL versus ABL, whereas GATA-3 expression was similar. Expression of T-bet and c-maf correlated with expression of the Th1 and Th2 cytokines, respectively. Time course experiments revealed that T-bet expression was stimulated in both cell types, whereas c-maf and GATA-3 were induced only in ABL.</p> <p>Conclusion</p> <p>The diminished capability of CBL to synthesize cytokines is probably due to decreased activation of NF-κB, whereas differences in Th subsets are due to differences in regulation of Th lineage-specific transcriptions factors. We propose that the reduced incidence and severity of GvHD after allogeneic transplantation of umbilical CB cells is due to lesser activation of specific transcription factors and a subsequent reduction in production of certain cytokines.</p

From gradual spreading to catastrophic collapse - Reconstruction of the 1888 Ritter Island volcanic sector collapse from high-resolution 3D seismic data

Volcanic island flank collapses have the potential to trigger devastating tsunamis threatening coastal communities and infrastructure. The 1888 sector collapse of Ritter Island, Papua New Guinea (in the following called Ritter) is the most voluminous volcanic island flank collapse in historic times. The associated tsunami had run-up heights of more than 20 m on the neighboring islands and reached settlements 600 km away from its source. This event provides an opportunity to advance our understanding of volcanic landslide-tsunami hazards. Here, we present a detailed reconstruction of the 1888 Ritter sector collapse based on high-resolution 2D and 3D seismic and bathymetric data covering the failed volcanic edifice and the associated mass-movement deposits. The 3D seismic data reveal that the catastrophic collapse of Ritter occurred in two phases: (1) Ritter was first affected by deep-seated, gradual spreading over a long time period, which is manifest in pronounced compressional deformation within the volcanic edifice and the adjacent seafloor sediments. A scoria cone at the foot of Ritter acted as a buttress, influencing the displacement and deformation of the western flank of the volcano and causing shearing within the volcanic edifice. (2) During the final, catastrophic phase of the collapse, about 2.4 km³ of Ritter disintegrated almost entirely and travelled as a highly energetic mass flow, which incised the underlying sediment. The irregular topography west of Ritter is a product of both compressional deformation and erosion. A crater-like depression underlying the recent volcanic cone and eyewitness accounts suggest that an explosion may have accompanied the catastrophic collapse. Our findings demonstrate that volcanic sector collapses may transform from slow gravitational deformation to catastrophic collapse. Understanding the processes involved in such a transformation is crucial for assessing the hazard potential of other volcanoes with slowly deforming flanks such as Mt. Etna or Kilauea

Assessment of “Gene-Environment” Interaction in Cases of Familial & Sporadic Pancreatic Cancer

Background: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. Reported risk factors for PC include: advancing age, a family history of PC, high-risk inherited syndromes, cigarette smoking, exposure to occupational and environmental carcinogens, African-American race, high fat/high cholesterol diet, obesity, chronic pancreatitis, and diabetes mellitus. Purpose: The purpose of this study was to characterize one of the largest national registries of familial PC (FPC) and sporadic PC (SPC), focusing on demographics, clinical factors, self-reported environmental and occupational lifetime exposures and survival status. Methods: Retrospective cross-sectional, case-only analysis of FPC cases (n = 569) and SPC cases (n = 689) from the Johns Hopkins National Familial Pancreas Tumor Registry (NFPTR) enrolled between 1994 and 2005

Time course of transcription factor induction after stimulation with TPA and ionomycin

<p><b>Copyright information:</b></p><p>Taken from "Cytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors"</p><p>http://www.biomedcentral.com/1471-2172/8/18</p><p>BMC Immunology 2007;8():18-18.</p><p>Published online 31 Aug 2007</p><p>PMCID:PMC2018703.</p><p></p> ABL and CBL were harvested at different time points by lysing cells. mRNA levels were determined for T-bet (A), GATA-3 (B), and c-maf (C). Data points are mean ± standard error for 6 donors. *< 0.05 ABL vs. CBL

Induction of transcription factors in ABL and CBL after stimulation for 4 hrs

<p><b>Copyright information:</b></p><p>Taken from "Cytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors"</p><p>http://www.biomedcentral.com/1471-2172/8/18</p><p>BMC Immunology 2007;8():18-18.</p><p>Published online 31 Aug 2007</p><p>PMCID:PMC2018703.</p><p></p> mRNA levels of T-bet (A), GATA-3 (B), and c-maf (C) were determined using real-time RT-PCR. Data are expressed as arbitrary units normalized to β-actin to correct for RNA quantity and integrity. Columns are the mean ± standard for 3 donors. The inset shows the correlation between expression of the respective transcription factor with IFNγ and IL-4. Dotted line indicates basal transcript levels. Iono – Ionomycin

Kinetics of cytokine induction after stimulation with TPA and ionomycin

<p><b>Copyright information:</b></p><p>Taken from "Cytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors"</p><p>http://www.biomedcentral.com/1471-2172/8/18</p><p>BMC Immunology 2007;8():18-18.</p><p>Published online 31 Aug 2007</p><p>PMCID:PMC2018703.</p><p></p> ABL and CBL were harvested at different time points by lysing cells. mRNA levels for IFNγ (A), IL-4 (B), and IL-3 (C) were determined as in Figure 1. Data points are the mean ± standard error for 6 donors. *< 0.05, **< 0.01 ABL vs. CBL