271 research outputs found
PDE8 Regulates Rapid Teff Cell Adhesion and Proliferation Independent of ICER
BACKGROUND: Abolishing the inhibitory signal of intracellular cAMP by phosphodiesterases (PDEs) is a prerequisite for effector T (Teff) cell function. While PDE4 plays a prominent role, its control of cAMP levels in Teff cells is not exclusive. T cell activation has been shown to induce PDE8, a PDE isoform with 40- to 100-fold greater affinity for cAMP than PDE4. Thus, we postulated that PDE8 is an important regulator of Teff cell functions. METHODOLOGY/PRINCIPAL FINDINGS: We found that Teff cells express PDE8 in vivo. Inhibition of PDE8 by the PDE inhibitor dipyridamole (DP) activates cAMP signaling and suppresses two major integrins involved in Teff cell adhesion. Accordingly, DP as well as the novel PDE8-selective inhibitor PF-4957325-00 suppress firm attachment of Teff cells to endothelial cells. Analysis of downstream signaling shows that DP suppresses proliferation and cytokine expression of Teff cells from Crem-/- mice lacking the inducible cAMP early repressor (ICER). Importantly, endothelial cells also express PDE8. DP treatment decreases vascular adhesion molecule and chemokine expression, while upregulating the tight junction molecule claudin-5. In vivo, DP reduces CXCL12 gene expression as determined by in situ probing of the mouse microvasculature by cell-selective laser-capture microdissection. CONCLUSION/SIGNIFICANCE: Collectively, our data identify PDE8 as a novel target for suppression of Teff cell functions, including adhesion to endothelial cells
Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron
The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is . The combined inclusive and differential asymmetries are consistent with recent standard model predictions
Search for New Particles Decaying to b bbar in p pbar Collisions at sqrt{s}=1.8 TeV
We have used 87 pb^-1 of data collected with the Collider Detector at
Fermilab to search for new particles decaying to b bbar. We present
model-independent upper limits on the cross section for narrow resonances which
excludes the color-octet technirho in the mass interval 350 < M < 440 GeV/c^2.
In addition, we exclude topgluons, predicted in models of topcolor-assisted
technicolor, of width Gamma = 0.3 M in the mass range 280 < M < 670 GeV/c^2, of
width Gamma = 0.5 M in the mass range 340 < M < 640 GeV/c^2, and of width Gamma
= 0.7 M in the mass range 375 < M < 560 GeV/c^2.Comment: 17 pages in a LaTex generated postscript file, with one table and
four figures. Resubmitted to Physical Review Letters. Minor clarifications
were added to the text. The displayed normalization of the resonance models
in Figure 2 was modified to correspond to our 95% CL upper limit on the cross
section (instead of arbitrary normalization which was used previously). All
results are identical to those in the previous submissio
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