55 research outputs found
CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II
The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2) and T-cell specific CXCR3 agonistic chemokines (Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11) in TNF-α-, IFN-γ-, and IL-1β-stimulated human alveolar epithelial cells type II (AEC-II). AEC-II constitutively expressed high level of CCL2 mRNA in vitro and in situ , and released CCL2 protein in vitro . Treatment of AEC-II with proinflammatory cytokines up-regulated both CCL2 mRNA expression and release of immunoreactive CCL2, whereas IFN-γ had no effect on CCL2 release. In contrast, CXCR3 agonistic chemokines were not detected in freshly isolated AEC-II or in non-stimulated epithelial like cell line A549. IFN-γ, alone or in combination with IL-1β and TNF-α resulted in an increase in CXCL10, CXCL11, and CXCL9 mRNA expression and generation of CXCL10 protein by AEC-II or A549 cells. CXCL10 gene expression and secretion were induced in dose-dependent manner after cytokine-stimulation of AEC-II with an order of potency IFN-γ>>IL-1β ≥ TNF-α. Additionally, we localized the CCL2 and CXCL10 mRNAs in human lung tissue explants by in situ hybridization, and demonstrated the selective effects of cytokines and dexamethasone on CCL2 and CXCL10 expression. These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response
Update on HHV-8-Associated Malignancies
The human herpesvirus 8 (HHV-8) is the oncogenic virus associated with Kaposi’s sarcoma (KS) and lymphoproliferative disorders, namely, primary effusion lymphoma and multicentric Castleman’s disease. KS is among the most common malignancies seen in HIV-infected patients despite the decreased incidence of KS in the era of highly active antiretroviral therapy. Advances in molecular pathology reveal HHV-8 tumorigenesis is mediated through molecular mimicry wherein viral-encoded proteins can activate several cellular signaling cascades while evading immune surveillance. This knowledge has led to the evolution of multiple therapeutic strategies against specific molecular targets. Many such therapeutic modalities have shown activity, but none have proven to be curative. Identifying possible prognostic factors is another active area of research. This review summarizes the recent developments in the fields of virus transmission, molecular biology, and treatment of HHV-8-related neoplasms
Quantum Spacetime Phenomenology
I review the current status of phenomenological programs inspired by
quantum-spacetime research. I stress in particular the significance of results
establishing that certain data analyses provide sensitivity to effects
introduced genuinely at the Planck scale. And my main focus is on
phenomenological programs that managed to affect the directions taken by
studies of quantum-spacetime theories.Comment: 125 pages, LaTex. This V2 is updated and more detailed than the V1,
particularly for quantum-spacetime phenomenology. The main text of this V2 is
about 25% more than the main text of the V1. Reference list roughly double
Modern tests of Lorentz invariance
Motivated by ideas about quantum gravity, a tremendous amount of effort over
the past decade has gone into testing Lorentz invariance in various regimes.
This review summarizes both the theoretical frameworks for tests of Lorentz
invariance and experimental advances that have made new high precision tests
possible. The current constraints on Lorentz violating effects from both
terrestrial experiments and astrophysical observations are presented.Comment: Modified and expanded discussions of various points. Numerous
references added. Version matches that accepted by Living Reviews in
Relativit
The Confrontation between General Relativity and Experiment
The status of experimental tests of general relativity and of theoretical
frameworks for analysing them is reviewed. Einstein's equivalence principle
(EEP) is well supported by experiments such as the Eotvos experiment, tests of
special relativity, and the gravitational redshift experiment. Future tests of
EEP and of the inverse square law are searching for new interactions arising
from unification or quantum gravity. Tests of general relativity at the
post-Newtonian level have reached high precision, including the light
deflection, the Shapiro time delay, the perihelion advance of Mercury, and the
Nordtvedt effect in lunar motion. Gravitational-wave damping has been detected
in an amount that agrees with general relativity to better than half a percent
using the Hulse-Taylor binary pulsar, and other binary pulsar systems have
yielded other tests, especially of strong-field effects. When direct
observation of gravitational radiation from astrophysical sources begins, new
tests of general relativity will be possible.Comment: 89 pages, 8 figures; an update of the Living Review article
originally published in 2001; final published version incorporating referees'
suggestion
Varying constants, Gravitation and Cosmology
Fundamental constants are a cornerstone of our physical laws. Any constant
varying in space and/or time would reflect the existence of an almost massless
field that couples to matter. This will induce a violation of the universality
of free fall. It is thus of utmost importance for our understanding of gravity
and of the domain of validity of general relativity to test for their
constancy. We thus detail the relations between the constants, the tests of the
local position invariance and of the universality of free fall. We then review
the main experimental and observational constraints that have been obtained
from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites
dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic
microwave background and big bang nucleosynthesis. At each step we describe the
basics of each system, its dependence with respect to the constants, the known
systematic effects and the most recent constraints that have been obtained. We
then describe the main theoretical frameworks in which the low-energy constants
may actually be varying and we focus on the unification mechanisms and the
relations between the variation of different constants. To finish, we discuss
the more speculative possibility of understanding their numerical values and
the apparent fine-tuning that they confront us with.Comment: 145 pages, 10 figures, Review for Living Reviews in Relativit
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