Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous delivery of adenovirus vectors requires that the virus is not inactivated in the bloodstream. Serum neutralizing activity is well documented, but we show here that type 5 adenovirus also interacts with human blood cells. Over 90% of a typical virus dose binds to human (but not murine) erythrocytes ex vivo, and samples from a patient administered adenovirus in a clinical trial showed that over 98% of viral DNA in the blood was cell associated. In contrast, nearly all viral genomes in the murine bloodstream are free in the plasma. Adenovirus bound to human blood cells fails to infect A549 lung carcinoma cells, although dilution to below 1.7 x 10(7) blood cells/ml relieves this inhibition. Addition of blood cells can prevent infection by adenovirus that has been prebound to A549 cells. Adenovirus also associates with human neutrophils and monocytes ex vivo, particularly in the presence of autologous plasma, giving dose-dependent transgene expression in CD14-positive monocytes. Finally, although plasma with a high neutralizing titer (defined on A549 cells) inhibits monocyte infection, weakly neutralizing plasma can actually enhance monocyte transduction. This may increase antigen presentation following intravenous injection, while blood cell binding may both decrease access of the virus to extravascular targets and inhibit infection of cells to which the virus does gain access.
Mol Ther 2006 Jul
PMID:Adenovirus type 5 interactions with human blood cells may compromise systemic delivery. 1658 Aug 83

Bone marrow cell implantation (BMI) has been utilized to treat patients with limb and heart ischemia. BMI provides angiogenic precursors and angiogenic cytokine-producing cells, especially erythroid cells. In this study, we induced in vitro angiogenesis cultures and in vivo BMI simulation using a murine limb ischemia model to examine the role of erythroid cells and the effect of erythropoietin (EPO). Human erythroid colonies (BFU-e) induced capillary networks around the colonies in vitro. Erythroid cells in human bone marrow produced vascular endothelial growth factor and placental growth factor. The angiogenic effects of erythroid cells were further amplified in the presence of EPO. Limb-ischemic mice were treated with BMI +/- EPO, and limb survival, blood flow recovery, and muscle histology were analyzed. Treatment with whole bone marrow cells + EPO significantly improved limb survival and blood flow. The cumulative effects of EPO on BMI induced and increase in capillary number and artery enlargement. Erythroid cells were essential for the in vivo effects of BMI, and CD14-positive cells supported the biological effects. In addition to the direct effect of EPO on angiogenesis, EPO showed indirect effect on angiogenesis through amplifying the angiogenic effects by erythroid cells supported by CD14-positive cells.
J Mol Cell Cardiol 2006 May
PMID:Erythroid cells play essential roles in angiogenesis by bone marrow cell implantation. 1660 82

The lipopolysaccharide (LPS) of Gram-negative bacteria induces the expression of cytokines and proinflammatory genes via the TLR4 signaling pathway in diverse cell types. The purpose of the present study was to test the hypothesis that the nasopharynx epithelial cells (NECs) could recognize and respond to LPS. The underlying molecular mechanisms were further elucidated in the NEC line 5-8F for its ability to activate the NFkappaB and TNF-alpha reporter genes, in response to LPS. After LPS stimulation, the TNF-alpha promoter activity and the relevant production of TNF-alpha were significantly increased in 5-8F cells. Moreover, LPS activated NFkappaB p65, ERK1/2 and JNK1/2 and induced their translocation to the nucleus. Western blot analysis showed that the expression of NFkappaB p65, MEK1, ERK1/2, JNK1/2, phospho-ERK1/2 and phospho-JNK1/2 proteins also was increased in NEC 5-8F cells, following the LPS stimulation. Additionally, the expression of TLR1-6, MD2 and CD14 was examined by RT-PCR, and the CD14 expression was determined by flow cytometry analysis. We demonstrated that the expression of CD14, TLR4 and MD2 was crucial for the NEC responses to LPS. In conclusion, our results provide novel mechanisms for the response of nasopharnyx epithelial cells to LPS stimulation, through NFkappaB and MAPKs signaling pathways.
Mol Immunol 2007 Feb
PMID:Lipopolysaccharide (LPS) regulates TLR4 signal transduction in nasopharynx epithelial cell line 5-8F via NFkappaB and MAPKs signaling pathways. 1667 17

Adiponectin was revealed to have anti-atherogenic and anti-inflammatory properties and has been recently found to stimulate angiogenesis in vivo and in vitro. However, the role of adiponectin in endothelial differentiation remains unclear. The objective of this study was to investigate whether adiponectin can promote peripheral CD14(+) monocytes differentiation into endothelial cells (ECs). Human peripheral blood CD14(+) monocytes were cultured with or without adiponectin (10 microg/ml) for 10 days. Adiponectin significantly promoted EC morphology formation from CD14(+) monocytes. By flow cytometery analysis, cells treated with adiponection substantially increased mean fluorescence intensity of vascular endothelial growth factor receptor-2 (VEGFR-2) and endothelial nitric oxide synthase (eNOS), two specific endothelial markers, by 49.2 % and 53.9 %, respectively, as compared to control cells. By real time PCR analysis, the mRNA level of eNOS in adiponectin-treated cells was also increased by 31.9 % of that of the control cells. However, the mRNA levels of calponin and SMMHC, two specific SMC markers, in adiponectin-treated cells were decreased by 81.1 % and 79.7 % of that of the control cells, respectively. These data demonstrated that adiponectin could promote endothelial differentiation from peripheral blood CD14(+) monocytes by morphology change, upregulation of EC markers and downregulation of SMC markers. Adiponectin-promoted EC differentiation may contribute to vascular healing and angiogenesis.
J Cell Mol Med
PMID:Adiponectin promotes endothelial cell differentiation from human peripheral CD14+ monocytes in vitro. 1679 11

Synthetic triterpenoids, CDDO (2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid) or CDDO-imidazolide [2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid imidazolide (CDDO-Im)], induce cell differentiation in myeloid leukemia cells but their mechanism of action is not known. CDDO-Im induces monocytic differentiation markers, CD14, and nonspecific esterase in HL60 leukemia cells. We show that CDDO-Im activates the extracellular signal-regulated kinase (ERK) signaling pathway and up-regulates CCAAT/enhancer-binding protein beta, a transcription factor critical for monocytic differentiation. The monocytic differentiation induced by CDDO-Im was partially blocked by the mitogen-activated protein kinase/ERK kinase 1 inhibitor PD98059, suggesting that the mitogen-activated protein kinase-ERK1/2 pathway plays a role in the differentiation induced by CDDO-Im. Furthermore, CDDO-Im activates the transforming growth factor beta (TGF-beta)/Smad signaling pathway. CDDO-Im enhanced the phosphorylation of the receptor-regulated Smads, phospho-Smad3, and phospho-Smad1/5, but not phospho-Smad2, and induced the expression of Smad4. Monocytic differentiation induced by CDDO-Im was blocked by both TGF-beta antibody and the bone morphogenetic protein (BMP) antagonist Noggin. This indicates that activation of the Smad signaling pathway by triterpenoids is an important mechanism of monocytic differentiation. CDDO-Im induced the synthesis of mRNA for TGF-beta2, BMP6, TGF-beta type II receptor, and BMP type II receptor. CDDO-Im synergized with members of the TGF-beta superfamily or with 1alpha,25(OH)2vitamin D3 (D3) in monocytic differentiation, and the synergistic effect was particularly striking in combination with D3. The combination of triterpenoids and D3 may have a practical use in differentiation therapy of myeloid leukemia as well as for promoting the formation of bone and cartilage.
Mol Cancer Ther 2006 Jun
PMID:The synthetic triterpenoid CDDO-imidazolide induces monocytic differentiation by activating the Smad and ERK signaling pathways in HL60 leukemia cells. 1681 3

Nuclear receptors (NR) are key modulators of gene transcription. Their activity is ligand induced and modulates a large variety of tissue-specific cellular functions. However, for many NR little is known about their role in cells of the immune system. In this study, expression patterns and distribution of 24 NR were investigated in human peripheral blood mononuclear cells. We provide the first evidence of the expression of the 12 receptors CAR, CoupTFalpha, CoupTFbeta, FXR, GCNF, HNF4alpha, PPARbeta/delta, PXR, RevErbbeta, TR2, TR4 and TLX in highly purified CD4, CD8, CD19, CD14 cells. The expression profile of RevErbalpha and LXRalpha previously observed in B cell and macrophages, respectively, has been extended to CD4, CD8 and CD14 cells. Except for RARbeta, which was absence in any of the cells tested, our results suggest an almost ubiquitous expression of the NR in the different cell lineages of the immune system. The expression of CAR, CoupTFalpha, FXR was also confirmed at a protein level and despite conspicuous mRNA levels of HNF4alpha, only low levels of this receptor were detectable in the nuclear fraction of PBMCs. Expression of the latter receptors was mostly only a fraction (4-20%) of their expression in the thyroid gland, the adrenal gland, the lung or subcutaneous adipose tissue. The Spearman rank order correlation test was performed to examine the correlation in expression between individual nuclear receptor pairs in the four cell types for several donors. Distinct correlation patterns were observed between receptor pairs in the individual cell types. In CD4 T cells four NR, GCNF, PPARgamma, PPARalpha7 and RevErbbeta are perfectly correlated with each other (P> or =0.0167). In the other cell types correlations between NR pairs were more diverse, but also statistically highly significant. Interestingly, the relative expression level of a number of receptor pairs ranked identical or similar in at least three (CoupTFalpha and PPARbeta/delta, CoupTFbeta and HNF4alpha as well as RORbeta and PXR) or four cell types (CoupTFalpha and CoupTFbeta, PPARgamma and RevErbbeta). Despite the variability of NR expression in immune cells, these results suggest that some of the NR may be co-regulated in human immune cells.
Mol Immunol 2007 Feb
PMID:Nuclear receptors in human immune cells: expression and correlations. 1683 48

Ovulation is the complex, inflammatory-like process by which the cumulus oocyte complex (COC) is released from a mature, preovulatory follicle through a rupture site at the ovarian surface and requires expression of genes that generate and stabilize the expanded extracellular COC matrix. Gene profiling analyses of COCs at selected time intervals during ovulation revealed that many genes associated with immune related surveillance functions were also induced in cumulus cells. Specifically, cell surface signaling molecules known as pattern recognition receptors that act as sensors of the external environment important for the innate immune system to detect self from nonself or altered self are induced and/or expressed in cumulus cells as well as granulosa cells. These include the complement factor q1, CD14, and the Toll-like receptors (TLRs) 4, 8, and 9 as well as mediators of TLR activation, myeloid differentiation primary response gene 88 and interferon regulatory factor 3. COCs exposed to bacterial lipopolysaccharide exhibit enhanced phosphorylation of p38MAPK, ERK1/2 and nuclear factor-kappaB and increased expression of Il6 and Tnfa target genes, documenting that the TLR pathway is functional. Cumulus cells and granulosa cells also express the scavenger receptors CD36 and scavenger receptor type B1 and exhibited phagocytic uptake of fluorescently tagged bacterial particles. Collectively, these results provide novel evidence that cumulus cells as well as granulosa cells express innate immune related genes that may play critical roles in surveillance and cell survival during the ovulation process.
Mol Endocrinol 2006 Dec
PMID:Induced expression of pattern recognition receptors in cumulus oocyte complexes: novel evidence for innate immune-like functions during ovulation. 1693 71

The inflammatory phenotype of genetically modified mice is complex, and the role of Gram-negative lipopolysaccharide (LPS) in acute inflammation induced by surgical cannulation trauma, alone or in combination with hemorrhage and resuscitation ("hemorrhagic shock"), is both complex and controversial. We sought to determine if a mathematical model of acute inflammation could elucidate both the phenotype of CD14-deficient (CD14(-/-)) mice--following LPS, cannulation, or hemorrhagic shock--and the role of LPS in trauma/hemorrhage-induced inflammation. A mathematical model of inflammation initially calibrated in wild-type (C57Bl/6) mice subjected to LPS, cannulation, and hemorrhagic shock was recalibrated in CD14(-/-) mice subjected to the same insults, yielding an ensemble of models that suggested specific differences at the cellular and molecular levels (for example, 43-fold lower activation of leukocytes by LPS). The CD14(-/-)-specific model ensemble could account for complex changes in inflammatory analytes in these mice following LPS treatment. Model prediction of similar organ damage in CD14(-/-) and wild-type mice subjected to cannulation alone or with hemorrhagic shock was verified in vivo (similar ALT levels). These studies suggest that LPS-CD14 responses do not cause inflammation in surgical trauma/hemorrhagic shock and demonstrate a novel use of combined in silico and in vivo methods to elucidate the complex inflammatory phenotype of genetically modified animals.
Mol Med
PMID:In silico and in vivo approach to elucidate the inflammatory complexity of CD14-deficient mice. 1695 60

The aim of this study is to establish a novel mouse model with high achievement and chimerism by in utero transplantation of human hematopoietic stem/progenitor cells and to explore the possibility that human adult hematopoietic stem/progenitor cells can differentiate into hepatocyte-like cells and partially repair the liver damage induced by carbon tetrachloride (CCl(4)). Mononuclear cells (MNCs) were isolated from fresh human umbilical cord blood (hUCB) and CD34(+) cells were enriched from the MNCs by magnetic cell isolation. These cells were injected respectively into the fetal mice at 11-13 days of gestation. At one month after birth, the specific markers of human cells, human alpha-satellite sequence (h17alpha), CD14, CD34, CD45, and GPA were detected by PCR and FACS. At three and six months after birth, the established human-mouse chimeras were administered with CCl(4) by intraperitoneal injection. The biochemical markers (ALT, AST, ALP, albumin) in serum were determined and human hepatocyte-specific proteins, such as human albumin, hepatocyte nuclear factor-4, hepatocyte-specific antigen, tryptophan 2,3-dioxygenase and alpha fetoprotein were analyzed by PCR, RT-PCR, real-time PCR and immunohistochemistry staining, respectively. More than 77% of recipients demonstrated human-mouse chimera. Significantly, hUCB hematopoietic stem/progenitor cells may differentiate into human hepatocyte-like cells with evidence of the expression of human hepatocyte-specific proteins as well as partially repair or protect liver damage induced by CCl(4). The mouse model described in this article provides a useful tool for the studies of regeneration of human hepatocyte-like cells from adult hematopoietic stem/ progenitor cells as well as facilitates the therapeutic potential for liver diseases or damage by in utero transplantation.
Int J Mol Med 2006 Oct
PMID:In utero transplantation of human hematopoietic stem/progenitor cells partially repairs injured liver in mice. 1696 16

Although standardized protocols are widely used for the generation of monocyte-derived immunostimulatory dendritic cells (DC(ims)), the inducibility of Th1 cells by DC(ims) may considerably differ. As a measure for the quality of DC(ims) generated from an individual donor at a certain time point, CD83 is used in combination with HLA-DR and CD86 to assess DC maturation. When phenotypically analyzing DC(ims), we identified a subpopulation ( approximately 60%) of CD83+, CD86+, and HLA-DR+ DC(ims) that co-expressed CD25. DC within a given DC(ims) preparation identified by lower expression of CD83 and by selective expression of CD14, however, did not co-express CD25. In order to establish CD25 as an additional maturation marker of DC(ims), we studied the DC phenotype of these cells as well as the DC-dependent T-cell proliferation and T-cell cytokine production profile after co-incubation with sorted CD25(high) and CD25(low) subpopulations of CD83+, HLA-DR+, CD86+ DC(ims). CD25(high) DC(ims) showed significant up-regulation of the DC activation molecule CD43 and induced increased levels of IL-2 secretion in allogeneic T-cells (170.7+/-86.7pg/mL) as compared to T-cells coincubated with CD25(low) DC(ims) (86.6+/-37.6pg/mL) [p=0.0224]. This was reflected by a significantly lower T-cell stimulatory capacity of CD25(low) DC(ims) (84.0% of CD25(high) DC(ims), 1:10 ratio; p=0.014) whereas the T-cell stimulatory capacity of CD25(low) DC(ims) was much higher when compared to IL-10 induced regulatory DC (55.3% of CD25(high) DC(ims); 1:10 ratio). With regard to cancer vaccination protocols, we propose to use CD25 and CD43 as additional markers for DC quality control, assessment of maturational status, and positive selection.
Mol Immunol 2007 Mar
PMID:Enhanced T-cell activation and T-cell-dependent IL-2 production by CD83+, CD25high, CD43high human monocyte-derived dendritic cells. 1702 48


<< Previous 1 2 3 4 5 6 7 8 9 10