共查询到20条相似文献,搜索用时 0 毫秒
1.
Leung JY Chapman JA Harris JA Hale D Chung RS West AK Chuah MI 《Cellular and molecular life sciences : CMLS》2008,65(17):2732-2739
Olfactory ensheathing cells (OECs) have been shown previously to express Toll-like receptors and to respond to bacteria by translocating nuclear factor-kappaB from the cytoplasm to the nucleus. In this study, we show that OECs extended significantly more pseudopodia when they were exposed to Escherichia coli than in the absence of bacteria (p=0.019). Co-immunoprecipitation showed that E. coli binding to OECs was mediated by Toll-like receptor 4. Lyso-Tracker, a fluorescent probe that accumulates selectively in lysosomes, and staining for type 1 lysosome-associated membrane proteins demonstrated that endocytosed FITC-conjugated E. coli were translocated to lysosomes. They appeared to be subsequently broken down, as shown by transmission electron microscopy. No obvious adherence to the membrane and less phagocytosis was observed when OECs were incubated with inert fluorescent microspheres. The ability of OECs to endocytose bacteria supports the notion that OECs play an innate immune function by protecting olfactory tissues from bacterial infection. 相似文献
2.
K. Mutyambizi C. L. Berger R. L. Edelson 《Cellular and molecular life sciences : CMLS》2009,66(5):831-840
Langerhans cells are immature skin-homing dendritic cells that furnish the epidermis with an immune surveillance system, and
translate information between the internal and external milieu. Dendritic cells, in particular Langerhans cells, are gaining
prominence as one of the potential principal players orchestrating the decision between immunity and tolerance. Langerhans
cells capture aberrant self-antigen and pathogen-derived antigen for display to the efferent immune response. Recent evidence
suggests redundancy in the antigen-presenting function of Langerhans cells, with dermal dendritic subsets capable of fulfilling
an analogous role. There is mounting evidence that Langerhans cells can cross-prime T cells to recognize antigens. Langerhans
cells are proposed to stimulate T regulatory cells, and are implicated in the pathogenesis of cutaneous T cell lymphoma.The
phenotype of Langerhans cells, which may be tolerogenic or immunogenic, appears to depend on their state of maturity, inciting
immunogen and cytokine environment, offering the potential for manipulation in immunotherapy.
Received 6 August 2008; received after revision 18 September 2008; accepted 13 October 2008 相似文献
3.
Junger WG 《Cellular and molecular life sciences : CMLS》2008,65(16):2528-2540
Chemotaxis allows polymorphonuclear neutrophils (PMN) to rapidly reach infected and inflamed sites. However, excessive influx of PMN damages host tissues. Better knowledge of the mechanisms that control PMN chemotaxis may lead to improved treatments of inflammatory diseases. Recent findings suggest that ATP and adenosine are involved in PMN chemotaxis. Therefore, these purinergic signaling processes may be suitable targets for novel therapeutic approaches to ameliorate host tissue damage. 相似文献
4.
K. L. Sand E. Knudsen J. Rolin Y. Al-Falahi A. A. Maghazachi 《Cellular and molecular life sciences : CMLS》2009,66(8):1446-1456
Glatiramer acetate (GA or Copaxone) is a drug used to treat experimental autoimmune encephalomyelitis in mice and multiple
sclerosis in human. Here, we describe a new mechanism of action for this drug. GA enhanced the cytolysis of human NK cells
against autologous and allogeneic immature and mature monocyte-derived dendritic cells (DCs). This drug reduced the percentages
of mature DCs expressing CD80, CD83, HLA-DR or HLA-I. In contrast, it did not modulate the percentages of NK cells expressing
NKG2D, NKp30, or NKp44. Nonetheless, anti-NKp30 or anti-CD86 inhibited GA-enhanced human NK cell lysis of immature DCs. Hence,
CD86, and NKp30 are important for NK cell lysis of immature DCs, whereas CD80, CD83, HLA-DR and HLA-I are important for the
lysis of mature DCs when GA is used as a stimulus. Further, GA inhibited the release of IFN-γ 24 h but increased the release
of TNF-α 48 h after incubation with NK cells.
Received 13 November 2008; received after revision 10 February 2009; accepted 18 February 2009 相似文献
5.
Berger W Steiner E Grusch M Elbling L Micksche M 《Cellular and molecular life sciences : CMLS》2009,66(1):43-61
The unique and evolutionary highly conserved major vault protein (MVP) is the main component of ubiquitous, large cellular
ribonucleoparticles termed vaults. The 100 kDa MVP represents more than 70% of the vault mass which contains two additional
proteins, the vault poly (ADP-ribose) polymerase (vPARP) and the telomerase-associated protein 1 (TEP1), as well as several
short untranslated RNAs (vRNA). Vaults are almost ubiquitously expressed and, besides chemotherapy resistance, have been implicated
in the regulation of several cellular processes including transport mechanisms, signal transmissions and immune responses.
Despite a growing amount of data from diverse species and systems, the definition of precise vault functions is still highly
complex and challenging. Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular
signal transduction and immune defence.
Received 27 June 2008; received after revision 25 July 2008; accepted 30 July 2008 相似文献
6.
The potential effects of synthetic unmethylated oligodeoxynucleotides (ODN) containing CpG motifs, mimicking bacterial DNA, has never been evaluated on the immune response in the teleost fish gilthead seabream (Sparus aurata), the most important fish species in Mediterranean aquaculture. First, binding and competition studies have demonstrated that binding is saturated and promiscuous, suggesting the participation of several receptors. Moreover, leucocyte cytotoxic (NCC) activity, production of ROIs (reactive oxygen intermediates), and expression of immune-relevant genes was greatly primed by ODNs. Focusing on the mechanism, the TLR9 gene is widely distributed in seabream tissues and differently regulated in vitro by several stimuli. Moreover, and for the first time in fish, TLR9 mRNA has been detected in lymphocytes as the main cell-source. To conclude, ODNs containing GACGTT, GTCGTT (optimal for mouse and human, respectively) or AACGTT motifs are the most potent inducers of seabream immunity, whilst the involvement of TLR9 is under debate. 相似文献
7.
8.
Lin CI Chen CN Huang MT Lee SJ Lin CH Chang CC Lee H 《Cellular and molecular life sciences : CMLS》2008,65(17):2740-2751
Lysophosphatidic acid (LPA) is a low-molecular-weight lipid growth factor, which binds to G-protein-coupled receptors. Previous studies have shown that LPA enhances vascular endothelial growth factor-A (VEGF-A) expression in cancer cells and promotes angiogenesis process. However, the roles of LPA in lymphatic vessel formation and lymphangiogenesis have not been investigated. Here, we demonstrated that LPA up-regulated VEGF-C mRNA and protein expressions in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression levels of lymphatic markers, including Prox-1, LYVE-1 and podoplanin, were enhanced in LPA-stimulated tube forming endothelial cells in vitro and in vivo. Moreover, we showed that pretreatment with MAZ51, a VEGFR-3 kinase inhibitor, and introduction of VEGFR-3 siRNA suppressed LPA-induced HUVEC tube formation and lymphatic marker expressions. These results demonstrated that LPA enhances expression of lymphatic markers through activating VEGF-C receptors in endothelial cells. This study provides basic information that LPA might be a target for therapeutics against lymphangiogenesis and tumor metastasis. 相似文献
9.
Physiological arousal: a role for hypothalamic systems 总被引:5,自引:0,他引:5
The lateral hypothalamus (LH) has long been known as a homeostasis center of the brain that modulates feeding behavior, arousal and reward. The hypocretins (Hcrts, also called orexins) and melanin-concentrating hormone (MCH) are neuropeptides produced in two intermingled populations of a few thousand neurons in the LH. The Hcrts have a prominent role in regulating the stability of arousal, since Hcrt system deficiency leads to narcolepsy. MCH is an important modulator of energy balance, as MCH system deficiency in mice leads to leanness and increased metabolism. Recently, MCH has been proposed to modulate rapid eye movement sleep in rodents. In this review, we propose a working model of the cross-talk between Hcrt and MCH circuits that may provide an arousal balance system to regulate complex goal-oriented behaviors. 相似文献
10.
Molecular mechanisms of phagocytic uptake in mammalian cells 总被引:2,自引:1,他引:1
Groves E Dart AE Covarelli V Caron E 《Cellular and molecular life sciences : CMLS》2008,65(13):1957-1976
Phagocytosis is a highly conserved, complex process that has evolved to counter the constant threat posed by pathogens, effete cells and debris. Classically defined as a mechanism for internalising and destroying particles greater than 0.5 mum in size, it is a receptor-mediated, actin-driven process. The best-studied phagocytic receptors are the opsono-receptors, FcgammaR and CR3. Phagocytic uptake involves actin dynamics including polymerisation, bundling, contraction, severing and depolymerisation of actin filaments. Recent evidence points to the importance of membrane remodelling during phagocytosis, both in terms of changes in lipid composition and delivery of new membrane to the sites of particle binding. Here we review the molecular mechanisms of phagocytic uptake and some of the strategies developed by microbial pathogens to manipulate this process. 相似文献
11.
Antigen presentation by CD1 molecules and the generation of lipid-specific T cell immunity 总被引:2,自引:0,他引:2
It is now well demonstrated that the repertoire of T cells includes not only cells that recognize specific MHC-presented peptide antigens, but also cells that recognize specific self and foreign lipid antigens. This T cell recognition of lipid antigens is mediated by a family of conserved MHC class I-like cell surface glycoproteins known as CD1 molecules. These are specialized antigen-presenting molecules that directly bind a wide variety of lipids and present them for T cell recognition at the surface of antigen-presenting cells. Distinct populations of T cells exist that recognize CD1-presented lipids of microbial, environmental or self origin, and these T cells participate in immune responses associated with infectious, neoplastic, autoimmune and allergic diseases. Here we review the current knowledge of the biology of the CD1 system, including the structure, biosynthesis and trafficking of CD1 molecules, the structures of defined lipid antigens and the types of functional responses mediated by T cells specific for CD1-presented lipids. 相似文献
12.
D. E. Dye S. Karlen B. Rohrbach O. Staub L. R. Braathen K. A. Eidne D. R. Coombe 《Cellular and molecular life sciences : CMLS》2009,66(4):681-696
hShroom1 (hShrm1) is a member of the Apx/Shroom (Shrm) protein family and was identified from a yeast two-hybrid screen as
a protein that interacts with the cytoplasmic domain of melanoma cell adhesion molecule (MCAM). The characteristic signature
of the Shrm family is the presence of a unique domain, ASD2 (Apx/Shroom domain 2). mRNA analysis suggests that hShrm1 is expressed
in brain, heart, skeletal muscle, colon, small intestine, kidney, placenta and lung tissue, as well a variety of melanoma
and other cell lines. Co-immunoprecipitation and bioluminescence resonance energy transfer (BRET) experiments indicate that
hShrm1 and MCAM interact in vivo and by immunofluorescence microscopy some co-localization of these proteins is observed. hShrm1 partly co-localises with
β-actin and is found in the Triton X-100 insoluble fraction of melanoma cell extracts. We propose that hShrm1 is involved
in linking MCAM to the cytoskeleton.
D. E. Dye, S. Karlen: These authors contributed equally to this work.
Received 09 October 2008; received after revision 23 November 2008; accepted 09 December 2008 相似文献
13.
Terpenoids: natural inhibitors of NF-κB signaling with anti-inflammatory and anticancer potential 总被引:1,自引:0,他引:1
Salminen A Lehtonen M Suuronen T Kaarniranta K Huuskonen J 《Cellular and molecular life sciences : CMLS》2008,65(19):2979-2999
Traditional medicine has been a fertile source for revealing novel lead molecules for modern drug discovery. In plants, terpenoids
represent a chemical defense against environmental stress and provide a repair mechanism for wounds and injuries. Interestingly,
effective ingredients in several plant-derived medicinal extracts are also terpenoid compounds of monoterpenoid, sesquiterpenoid,
diterpenoid, triterpenoid and carotenoid groups. Inflammatory diseases and cancer are typical therapeutic indications of traditional
medicines. Thus folk medicine supports the studies which have demonstrated that plant-derived terpenoid ingredients can suppress
nuclear factor-κB (NF-κB) signaling, the major regulator in the pathogenesis of inflammatory diseases and cancer.We review
the extensive literature on the different types of terpenoid molecules, totalling 43, which have been verified both inhibiting
the NF-κB signaling and suppressing the process of inflammation and cancer. It seems that during evolution, plants have established
a terpene-based host defense which also represents a cornucopia of effective therapeutic compounds for common human diseases.
Received 11 March 2008; received after revision 28 April 2008; accepted 29 April 2008 相似文献
14.
A. Gerson-Gurwitz N. Movshovich R. Avunie V. Fridman K. Moyal B. Katz M. A. Hoyt L. Gheber 《Cellular and molecular life sciences : CMLS》2009,66(2):301-313
S. cerevisiae anaphase spindle elongation is accomplished by the overlapping function of dynein and the kinesin-5 motor proteins, Cin8
and Kip1. Cin8 and dynein are synthetically lethal, yet the arrest phenotypes of cells eliminated for their function had not
been identified. We found that at a non-permissive temperature, dyn1Δ cells that carry a temperature-sensitive cin8 – 3 mutation arrest at mid-anaphase with a unique phenotype, which we named TAN (two microtubule asters in one nucleus). These
cells enter anaphase, but fail to proceed through the slow phase of anaphase B. At a permissive temperature, dyn1Δ, cin8 – 3 or dyn1Δcin8 – 3 cells exhibit perturbed spindle midzone morphologies, with dyn1Δcin8 – 3 anaphase spindles also being profoundly bent and nonrigid. Sorbitol, which has been suggested to stabilize microtubules,
corrects these defects and suppresses the TAN phenotype. We conclude that dynein and Cin8 cooperate in anaphase midzone organization
and influence microtubule dynamics, thus enabling progression through the slow phase of anaphase B.
Received 10 August 2008; received after revision 22 October 2008; accepted 27 October 2008 相似文献
15.
Inoue K 《Cellular and molecular life sciences : CMLS》2008,65(19):3074-3080
Accumulating findings indicate that nucleotides play an important role in microglia through P2 purinoceptors. P2 purinoceptors
are divided into two families, ionotropic receptors (P2X) and metabotropic receptors (P2Y). P2X receptors (7 types; P2X1 – P2X7) contain intrinsic pores that open by binding with ATP. P2Y receptors (8 types; P2Y1, 2, 4, 6, 11, 12, 13 and 14) are activated by nucleotides and couple to intracellular second-messenger systems through heteromeric G-proteins. Nucleotides
are released or leaked from non-excitable cells as well as neurons in physiological and pathophysiological conditions. Microglia
express many types of P2 purinoceptors and are known as resident macrophages in the CNS. ATP and other nucleotides work as
‘warning molecules’ especially through activating microglia in pathophysiological conditions. Microglia play a key role in
neuropathic pain, chemotaxis and phagocytosis through nucleotide-evoked activation of P2X4, P2Y12 and P2Y6 receptors, respectively. These findings indicate that extracellular nucleotides are important players in the central stage
of microglial function.
Received 19 April 2008; received after revision 20 May 2008; accepted 23 May 2008 相似文献
16.
S. Wilde E. Schlatter H. Koepsell B. Edemir S. Reuter H. Pavenstädt U. Neugebauer R. Schröter S. Brast G. Ciarimboli 《Cellular and molecular life sciences : CMLS》2009,66(10):1729-1740
In this work, regulation of organic cation transporter type 2 from rat (rOCT2) stably transfected in HEK293 cells was investigated
by microfluorimetry with 4-(4-(dimethylamino)styryl)-N-methylpyridinium as substrate. The transport mediated by rOCT2 was
specifically stimulated by PKA, phosphatidylinositol-3-kinase, p56lck tyrosine kinase, mitogen-extracellular-signal-regulated-kinase-1/2, calmodulin (CaM), and CaM-kinase-II. The regulatory pattern
of rOCT2 differs markedly quantitatively and qualitatively from that of other OCT isoforms. Only CaM-dependent upregulation
is conserved throughout the OCT family. For this reason, CaM regulation of rOCT2 was also investigated in isolated S3-segments
(known to express only rOCT2) of male and female rat proximal tubules. Inhibition of CaM by calmidazolium significantly decreased
rOCT2 activity (−49.0 ± 13.6%, n = 4) in male but not female (9.0 ± 13.0%, n = 4) rats. Real-time PCR and Western blot investigations
of CaM expression in rat kidneys showed that male animals have significantly higher CaM expression. This is the first study
describing post-translational gender-dependent rOCT2 regulation.
Received 26 February 2009; accepted 16 March 2009 相似文献
17.
18.
Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease. 相似文献
19.
Glutamate, by activation of metabotropic receptors (mGluRs), can lead to a reduction of synaptic efficacy at many synapses.
These forms of synaptic plasticity are referred to as long-term depression (mGluR-LTD). We will distinguish between mGluR-LTD
induced by pre- or postsynaptic receptors and mGluR-LTD induced by the locus of the expression mechanism of the synaptic depression.
We will also review recent evidence that mGluR-mediated responses themselves are subject to depression, which may constitute
a form of metaplasticity.
Received 13 May 2008; received after revision 07 July 2008; accepted 11 July 2008 相似文献
20.