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991.
Zafirova B Wensveen FM Gulin M Polić B 《Cellular and molecular life sciences : CMLS》2011,68(21):3519-3529
NKG2D is one of the most intensively studied immune receptors of the past decade. Its unique binding and signaling properties,
expression pattern, and functions have been attracting much interest within the field due to its potent antiviral and anti-tumor
properties. As an activating receptor, NKG2D is expressed on cells of the innate and adaptive immune system. It recognizes
stress-induced MHC class I-like ligands and acts as a molecular sensor for cells jeopardized by viral infections or DNA damage.
Although the activating functions of NKG2D have been well documented, recent analysis of NKG2D-deficient mice suggests that
this receptor may have a regulatory role during NK cell development. In this review, we will revisit known aspects of NKG2D
functions and present new insights in the proposed influence of this molecule on hematopoietic differentiation. 相似文献
992.
993.
Terhi Vihervaara Riikka-Liisa Uronen Gerd Wohlfahrt Ingemar Björkhem Elina Ikonen Vesa M. Olkkonen 《Cellular and molecular life sciences : CMLS》2011,68(3):537-551
ORP1L is an oxysterol binding homologue that regulates late endosome (LE) positioning. We show that ORP1L binds several oxysterols
and cholesterol, and characterize a mutant, ORP1L Δ560–563, defective in oxysterol binding. While wild-type ORP1L clusters
LE, ORP1L Δ560–563 induces LE scattering, which is reversed by disruption of the endoplasmic reticulum (ER) targeting FFAT
motif, suggesting that it is due to enhanced LE–ER interactions. Endosome motility is reduced upon overexpression of ORP1L.
Both wild-type ORP1L and the Δ560–563 mutant induce the recruitment of both dynactin and kinesin-2 on LE. Most of the LE decorated
by overexpressed ORP1L fail to accept endocytosed dextran or EGF, and the transfected cells display defective degradation
of internalized EGF. ORP1L silencing in macrophage foam cells enhances endosome motility and results in inhibition of [3H]cholesterol efflux to apolipoprotein A-I. These data demonstrate that LE motility and functions in both protein and lipid
transport are regulated by ORP1L. 相似文献
994.
Proline-rich antimicrobial peptides are a group of cationic host defense peptides of vertebrates and invertebrates characterized
by a high content of proline residues, often associated with arginine residues in repeated motifs. Those isolated from some
mammalian and insect species, although not evolutionarily related, use a similar mechanism to selectively kill Gram-negative
bacteria, with a low toxicity to animals. Unlike other types of antimicrobial peptides, their mode of action does not involve
the lysis of bacterial membranes but entails penetration into susceptible cells, where they then act intracellularly. Some
aspects of the transport system and cytoplasmic targets have been elucidated. These features make them attractive both as
anti-infective lead compounds and as a new class of potential cell-penetrating peptides capable of internalising membrane-impermeant
drugs into both bacterial and eukaryotic cells 相似文献
995.
Wesch D Peters C Oberg HH Pietschmann K Kabelitz D 《Cellular and molecular life sciences : CMLS》2011,68(14):2357-2370
Toll-like receptors (TLR) are pattern-recognition receptors that recognize a broad variety of structurally conserved molecules
derived from microbes. The recognition of TLR ligands functions as a primary sensor of the innate immune system, leading to
subsequent indirect activation of the adaptive immunity as well as none-immune cells. However, TLR are also expressed by several
T cell subsets, and the respective ligands can directly modulate their effector functions. The present review summarizes the
recent findings of γδ T cell modulation by TLR ligands. TLR1/2/6, 3, and 5 ligands can act directly in combination with T
cell receptor (TCR) stimulation to enhance cytokine/chemokine production of freshly isolated human γδ T cells. In contrast
to human γδ T cells, murine and bovine γδ T cells can directly respond to TLR2 ligands with increased proliferation and cytokine
production in a TCR-independent manner. Indirect stimulatory effects on IFN-γ production of human and murine γδ T cells via
TLR-ligand activated dendritic cells have been described for TLR2, 3, 4, 7, and 9 ligands. In addition, TLR3 and 7 ligands
indirectly increase tumor cell lysis by human γδ T cells, whereas ligation of TLR8 abolishes the suppressive activity of human
tumor-infiltrating Vδ1 γδ T cells on αβ T cells and dendritic cells. Taken together, these data suggest that TLR-mediated
signals received by γδ T cells enhance the initiation of adaptive immune responses during bacterial and viral infection directly
or indirectly. Moreover, TLR ligands enhance cytotoxic tumor responses of γδ T cells and regulate the suppressive capacity
of γδ T cells. 相似文献
996.
Ververis K Rodd AL Tang MM El-Osta A Karagiannis TC 《Cellular and molecular life sciences : CMLS》2011,68(24):4101-4114
Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid
(Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that
histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies
such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies,
involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified
that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in
cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase
inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes.
Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors
tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained
nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight
the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination
therapies for cancer. 相似文献
997.
Tsai S Clemente-Casares X Santamaria P 《Cellular and molecular life sciences : CMLS》2011,68(23):3781-3795
Autoreactive CD8+ regulatory T cells (Tregs) play important roles as modulators of immune responses against self, and numerical and functional
defects in CD8+ Tregs have been linked to autoimmunity. Several subsets of CD8+ Tregs have been described. However, the origin of these T cells and how they participate in the natural progression of autoimmunity
remain poorly defined. We discuss several lines of evidence suggesting that the autoimmune process itself promotes the development
of autoregulatory CD8+ T cells. We posit that chronic autoantigenic exposure fosters the differentiation of non-pathogenic autoreactive CD8+ T cells into antigen-experienced, memory-like autoregulatory T cells, to generate a “negative feedback” regulatory loop capable
of countering pathogenic autoreactive effectors. This hypothesis predicts that approaches capable of boosting autoregulatory
T cell memory will be able to blunt autoimmunity without compromising systemic immunity. 相似文献
998.
The maintenance of mucosal barrier equilibrium in the intestine requires a delicate and dynamic balance between enterocyte
loss by apoptosis and the generation of new cells by proliferation from stem cell precursors at the base of the intestinal
crypts. When the balance shifts towards either excessive or insufficient apoptosis, a broad range of gastrointestinal diseases
can manifest. Recent work from a variety of laboratories has provided evidence in support of a role for receptors of the innate
immune system, including Toll-like receptors 2, 4, and 9 as well as the intracellular pathogen recognition receptor NOD2/CARD15,
in the initiation of enterocyte apoptosis. The subsequent induction of enterocyte apoptosis in response to the activation
of these innate immune receptors plays a key role in the development of various intestinal diseases, including necrotizing
enterocolitis, Crohn’s disease, ulcerative colitis, and intestinal cancer. This review will detail the regulatory pathways
that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis
in gastrointestinal disease. 相似文献
999.
Wiring of vascular and neural networks requires precise guidance of growing blood vessels and axons, respectively, to reach
their targets during development. Both of the processes share common molecular signaling pathways. Transient receptor potential
canonical (TRPC) channels are calcium-permeable cation channels and gated via receptor- or store-operated mechanisms. Recent
studies have revealed the requirement of TRPC channels in mediating guidance cue-induced calcium influx and their essential
roles in regulating axon navigation and angiogenesis. Dissecting TRPC functions in these physiological processes may provide
therapeutic implications for suppressing pathological angiogenesis and improving nerve regeneration. 相似文献
1000.
Antimicrobial agents are toxic to bacteria by a variety of mechanisms. One mechanism that is very dependent on the lipid composition of the bacterial membrane is the clustering of anionic lipid by cationic antimicrobial agents. Certain species of oligo-acyl-lysine (OAK) antimicrobial agents are particularly effective in clustering anionic lipids in mixtures mimicking the composition of bacterial membranes. The clustering of anionic lipids by certain cationic antimicrobial agents contributes to the anti-bacterial action of these agents. Bacterial membrane lipids are a determining factor, resulting in some species of bacteria being more susceptible than others. In addition, lipids can be used to increase the effectiveness of antimicrobial agents when administered in vivo. Therefore, we review some of the structures in which lipid mixtures can assemble, to more effectively be utilized as antimicrobial delivery systems. We describe in more detail the complexes formed between mixtures of lipids mimicking bacterial membranes and an OAK and their usefulness in synergizing with antibiotics to overcome bacterial multidrug resistance. 相似文献