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1.
Science Letters: A synthetic Toll-like receptor 2 ligand decreases allergic immune responses in a mouse rhinitis model sensitized to mite allergen
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It has been proposed that activation of Toll-like receptors (TLRs) plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 (TLR2) ligand, Pam3CSK4, has been reported to modulate the balance of Th1/Th2 responses. We evaluated the modulation effect of Pam3CSK4 on allergic immune response in a mouse rhinitis model sensitized to house dust mite allergen (HDM). Mice were sensitized and challenged with Dermatophagoidesfarinae allergen (Der f), and then the allergic mice were treated by Pam3CSK4. Nasal allergic symptoms and eosinophils were scored. Der f-specific cytokine responses were examined in the splenocytes and bronchoalveolar lavage fluid (BALF). Serum level of total IgE was also detected. After establishing a mouse allergic rhinitis model with HDM, we have showed that Pam3CSK4 treatment not only ameliorated the nasal allergic symptoms remarkably but also decreased the eosinophils and total inflammation cells in BALF significantly. Analysis of cytokine profile found that IFN-7 released from either BALF or stimulated splenocytes increased markedly in Pam3CSK4-treated mice, while IL-13 decreased significantly. Moreover, serum level of total IgE was significantly lower in Pam3CSK4-treated mice than in the untreated. Thus, in an allergic rhinitis mouse model developed with HDM, Pam3CSK4 was shown to exhibit an antiallergic effect, indicating its potential application in allergic diseases. 相似文献
2.
《科学通报(英文版)》2008,(19)
The purposes of this research were to study the stable expression of exogenous gene encoding therapeutic protein in attenuated Salmonella typhimurium, observe the metabolism of oral gene vaccine carried by attenuated Salmonella typhimurium in BALB/c mouse, and investigate the feasibility of prevention and treatment of tumors by the recombinant bacteria. Recombinant plasmid pcDNA3.1 VEGFR2(n1-7) was transformed into competent attenuated Salmonella typhimurium SL3261 to develop oral DNA vaccine SL3261-pcDNA3.1 VEGFR2(n1-7). To observe whether the exogenous gene can be expressed in the recombinant bacteria, PCR was performed to amplify the CMV promoter of the eukaryotic expression vector as the proof of stable expression of exogenous protein; transmission elec- tron microscopy (TEM) was applied to observe the morphology of the recombinant bacteria to confirm that the exogenous gene has no impact on the growth of the bacteria, and then BALB/c mice were immunized with the gene vaccine. After inoculation of the gene vaccine, the recombinant bacteria SL3261 could be detected in the tissues such as small intestine, colon, liver and spleen. And then, mice in each group were challenged with tumor cells. The results of animal experiment showed that tumor growth of the mice in experimental group was inhibited and survival time of immunized mice was prolonged compared with control groups. A higher lymphocyte infiltration in tumors from animals treated with DNA vaccine was observed. Immunohistochemical analysis of tumor samples revealed an en- hanced accumulation of CD8 cytotoxic T lymphocytes, as well as an increase in CD4 cells in the tumors of animals treated with the oral gene vaccine compared to tumors from control group mice. Ultrastructure of the tumor tissue showed that tumor cells in the samples of the immunized mice were well-differentiated. Our research confirmed that the exogenous gene can be stably expressed in the attenuated Salmonella typhimurium and has no impact on the growth of the recombinant bacteria; the exogenous gene can de delivered to the host by attenuated Salmonella typhimurium to produce anti-tumor effect with no obvious cytotoxity to the host. In this study, it is established that attenuated Salmonella typhimurium could be used as a vector for oral gene vaccine, and our study provided a theoretical basis for the body distribution and the metabolism of the recombinant bacteria. This strategy may provide a simple, safe and effective way for the prevention and treatment of tumors. 相似文献
3.
Growth hormone signal transduction 总被引:1,自引:0,他引:1
Growth hormone (GH) promotes animal growth by stimulating bone and cartilage cell proliferation, and influences carbohydrate and lipid metabolism. Some of these effects are brought about indirectly via somatomedin induction in hepatocytes, others by acting directly on the target cells. In either case, GH first binds to specific receptors on cells to trigger a sequence of biochemical events culminating in a biological response. Recently much has been learnt about the molecular structure of GH receptor, its binding to ligand, and the ensuing signal transduction events. 相似文献
4.
M. T. Santini R. Masella A. Cantafora S. W. Peterson 《Cellular and molecular life sciences : CMLS》1992,48(1):36-39
We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T for a 3-h period at 37°C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation. 相似文献
5.
Colony-stimulating factor-1 (CSF-1), which is necessary for cell proliferation and differentiation, regulates both immediate
and delayed early responses throughout G1 phase. The binding of CSF-1 to its receptor (CSF-1R) triggers phosphorylation of
the receptor and its intrinsic tyrosine kinase. The activated receptor binds directly to cytoplasmic effector proteins, which
induce multiple-signal transduction pathways. CSF-1 can induce the c-myc gene expression via Ras and Ets-related proteins.
The expression of c-fos/jun family genes is also targeted following the activation of Ras. CSF-1R activates STAT1 and STAT3
to participate in signaling, but JAKs do not appear to contribute to signaling by CSF-1R. CSF-1R activates PI3-kinase, and
PI3-ki can interact with downstream proteins by the MAPKK-related pathway independent of Ras/Raf. PC-PLC can enforce signaling
in response to CSF-1. Furthermore, the turnover and dephosphorylation by the phosphatase SHPTP1 of CSF-1R are the major mechanism
in the negative regulation of signaling by CSF-1R 相似文献
6.
Radio ligand binding assays(RLBA) were used to study neuropeptide Y (NPY) receptors in a protozoa Stylonychia mytilus. The experimental results showed that 2-3×10+3/mL Stylonychia cells incubated in Pringsheim solution which contained 3H-NPY could specifically bind 3H-NPY and concomitantly present saturable characteristic. This suggested that Stylonychia possessed some specific binding sites for NPY. Scatchard transformations of binding assay for the NPY receptors at 25℃ are compatible with the specific activity of 42.47 fmol/10+3 cells and the binding equilibrium constant of 0.113 nmol/L. The data of 125I-NPY binding assay to the membrane protein extract of Stylonychia indicated that there was a significant difference between the amount of total bound and nonspecific bound of 125I-NPY. This result indicated that NPY receptors were probably localized mainly on the cell membrane. 相似文献
7.
Molecular evidence for increased hematopoietic proliferation in the spleen of the b/b laboratory rat
S. Savković S. Pavlović T. Mitrović M. Joksimović J. Marjanović V. Glišin Z. Popović 《Cellular and molecular life sciences : CMLS》1996,52(8):807-811
The splenomegaly and the appearance of a significant number of CFU-E (erythroid colony-forming units) and BFU-E1 (erythroid burst-forming units) in the Belgrade laboratory rat (b/b) spleen prompted us to analyse further the molecular evidence for increased hematopoietic proliferation in the b/b spleen. Messenger RNAs (mRNAs) specific for globins, proteins for iron transport and deposition and the band 3 protein were used in rat erythropoietic tissues as markers for proliferation and erythroid differentiation. In the b/b spleen, all mRNAs analysed display an erythroid-specific pattern of expression. This analysis also revealed an enhanced level of mRNA for ferritin in the +/b spleen, whereas erythrocyte-specific mRNA production was normal. 相似文献
8.
T. Matsuoka T. Nishizaki Y. Ikeuchi Y. Okada K. Sumino 《Cellular and molecular life sciences : CMLS》1997,53(3):233-236
Effects of serotonin (5-HT) on cerebral cortical neurons were examined by patch clamp techniques. 5-HT produced a variety
of responses such as outward (19/73 patches/neurons), slow inward (15/73 patches/neurons), fast inward (8/73 patches/neurons),
and mixed currents (initially fast inward deflection followed by an outward response: 2/73 patches/neurons), with a latency
of 12 sec, 15 sec, 0 sec, and 0 sec respectively, at a holding potential of −60 mV in whole-cell patches. The fast inward
currents were again evoked by a selective 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide hydrochloride (CPBG). In the
cell-attached patch clamp configuration, 5-HT inside the patch pipette elicited single channel currents with slope conductances
of 42 pS and 132 pS (4/42 patches/neurons). CPBG inside the patch pipette evoked inward single channel currents with a lower
slope conductance of 41 pS (3/23 patches/neurons). In contrast, application of 5-HT or a 5-HT2 receptor agonist, α-methyl-5-hydroxytryptamine-maleate, outside the patch pipette induced outward single channel currents with a major slope
conductance of 140 pS (8/30 patches/neurons) or 135 pS (6/20 patches/neurons), respectively. These results indicate that the
outward and fast inward currents may be mediated respectively by the 5-HT2 receptor, which is coupled to a G-protein, and by the 5-HT3 receptor, which contains the non-selective cation channel, and that the mixed type may be caused by both the 5-HT2 and 5-HT3 receptors.
Received 27 September 1996; received after revision 4 November 1996; accepted 7 November 1996 相似文献
9.
10.
以葡萄(VitisviniferaL.)的花药和花丝为实验材料,观察了葡萄离体培养中胚状体的发生发育过程.结果表明:(1)葡萄的花药和花丝经诱导都可形成胚性和非胚性两类不同的愈伤组织,与外植体来源无关,胚状体经胚性愈伤组织产生.(2)胚状体多起源于胚性愈伤组织表层或表层以下的单个细胞,这些细胞核大,细胞质浓,染色深,在表层者易于脱落而处于单个离散状态,它们的第一次分裂有均等分裂,也有不等分裂,经2细胞、3细胞、多细胞原胚等阶段发育为成熟的胚状体.(3)葡萄胚状体具有与双子叶植物合子胚相似的发育过程 相似文献