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71.
The Slc11a1 (Nramp1) gene controls efficacy of mycobacterial treatment of allergic asthma 总被引:2,自引:0,他引:2
Smit JJ Van Loveren H Hoekstra MO Karimi K Folkerts G Nijkamp FP 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(2):754-760
Genes controlling antibacterial resistance may be important in the hygiene hypothesis, which states that lack of bacterial infections during childhood would favor development of allergic disease. We, therefore, studied whether Nramp1 (Slc11a1) alleles, which determine susceptibility (Nramp1(s)) or resistance (Nramp1(r)) to intracellular bacteria, affect the efficacy of heat-killed Mycobacterium vaccae in the treatment of allergic asthma in a mouse model. Treatment of OVA-sensitized Nramp1(s) mice with M. vaccae suppressed airway hyperresponsiveness, airway eosinophilia, Ag-specific IgE, and IL-4 and IL-5 production after OVA aerosol challenge. In contrast, M. vaccae hardly affected these parameters in Nramp1(r) mice. In addition, The Nramp1 gene affected both T cell-mediated responses to M. vaccae in vivo and the level of macrophage activation after stimulation with M. vaccae in vitro. In conclusion, the efficacy of M. vaccae in preventing allergic and asthmatic manifestations in a mouse model is strongly affected by Nramp1 alleles. These findings could have important implications for the future use of mycobacteria and their components in the prevention or treatment of allergic asthma. A new link is described between genes, the environment, and the development of allergy, in which the Nramp1 gene fine tunes the hygiene hypothesis. 相似文献
72.
Bouillon M El Fakhry Y Girouard J Khalil H Thibodeau J Mourad W 《The Journal of biological chemistry》2003,278(9):7099-7107
Lipid rafts are plasma membrane microdomains that are highly enriched in signaling molecules and that act as signal transduction platforms for many immune receptors. The involvement of these microdomains in HLA-DR-induced signaling is less well defined. We examined the constitutive presence of HLA-DR molecules in lipid rafts, their possible recruitment into these microdomains, and the role of these microdomains in HLA-DR-induced responses. We detected significant amounts of HLA-DR molecules in the lipid rafts of EBV(+) and EBV(-) B cell lines, monocytic cell lines, transfected HeLa cells, tonsillar B cells, and human monocytes. Localization of HLA-DR in these microdomains was unaffected by the deletion of the cytoplasmic domain of both the alpha and beta chains. Ligation of HLA-DR with a bivalent, but not a monovalent, ligand resulted in rapid tyrosine phosphorylation of many substrates, especially Lyn, and activation of ERK1/2 MAP kinase. However, the treatment failed to induce further recruitment of HLA-DR molecules into lipid rafts. The HLA-DR-induced signaling events were accompanied by the induction of cell-cell adhesion that could be inhibited by PTK and Lyn but not ERK1/2 inhibitors. Disruption of lipid rafts by methyl-beta-cyclodextrin (MbetaCD) resulted in the loss of membrane raft association with HLA-DR molecules, inhibition of HLA-DR-mediated protein tyrosine phosphorylation and cell-cell adhesion. MbetaCD did not affect the activation of ERK1/2, which was absent from lipid rafts. These results indicate that although all the HLA-DR-induced events studied are dependent on HLA-DR dimerization, some require the presence of HLA-DR molecules in lipid rafts, whereas others do not. 相似文献
73.
Nuclear matrix, a key structure in the nuclear framework, appears to be a particularly responsive target during heat shock treatment of cells. We have previously shown that nuclear matrix is a preferential target for protein kinase CK2 signaling in the nucleus. The levels of CK2 in the nuclear matrix undergo dynamic changes in response to altered growth status in the cell. Here, we have demonstrated that CK2 targeting to the nuclear matrix is profoundly influenced by treatment of the cells to temperatures higher than 37 degrees C. Rapid increase in the nuclear matrix association of CK2 is observed when cells are placed at temperatures of 41 and 45 degrees C. This effect at 45 degrees C was higher than at 41 degrees C, and was time-dependent. Also, different cell lines behaved in a qualitatively similar manner though the quantitative responses differed. The modulations in the nuclear matrix associated CK2 in response to heat shock appear to be due to trafficking of the enzyme between cytosolic and nuclear compartments. In addition, it was noted that isolated nuclei subjected to heat shock also responded by a shuttling of the intrinsic CK2 to the nuclear matrix compartment. These results suggest that modulations in CK2 in the nuclear compartment in response to the heat stress occur not only by a translocation of the enzyme from the cytoplasmic compartment to the nuclear compartment, but also that there is a redistribution of the kinase within the nuclear compartment resulting in a preferential association with the nuclear matrix. The results support the notion that CK2 association with the nuclear matrix in response to heat shock may serve a protective role in the cell response to stress. 相似文献
74.
Honma M Namikawa K Mansur K Iwata T Mori N Iizuka H Kiyama H 《Journal of neurochemistry》2002,82(4):961-975
Axotomy-induced neuronal death occurs in neonatal motoneurons, but not in adult rat. Here we demonstrated that during the course of postnatal development, nerve injury induced down-regulation of the glial cell line-derived neurotrophic factor (GDNF) receptor GFRalpha1 in axotomized hypoglossal motoneurons of rat are gradually converted to the adult up-regulation pattern of response. The compensatory expression of GFRalpha1 specifically in the injured motoneurons of neonates by adenovirus succeeded in rescuing the injured neurons without an application of growth factors. To the contrary, the nuclear antisense RNA for GFRalpha1 expression accelerates the axotomy-induced neuronal death in pups. These findings suggest that the receptor expression response after nerve injury is critical for the determination of injured motoneuron fate. 相似文献
75.
The ligninolytic white-rot fungus Phanerochaete chrysosporium BKM-F-1767 produced extracellular cellulolytic enzymes (carboxymethylcellulase, CMCase and -glucosidase) and xylanolytic enzymes (xylanase and -xylosidase) in liquid medium containing 1.0% sugarcane bagasse with or without 1.0% glucose. The changes in pH and soluble protein content were monitored in the culture filtrates. The results obtained showed that the pH decreased after 3 days and then increased. The soluble protein content increased and reached the maximum value after 12 days. The results showed that the activities of enzymes were higher in the case of sugarcane bagasse without glucose. The characterization study indicated that the optimum pH values were 4.6, 4.2, 5.0 and 5.0 for CMCase, -glucosidase, xylanase and -xylosidase, respectively and the optimum temperatures were 60, 70, 65 and 60 °C for the investigated enzymes, respectively. The results showed also that after prolonged heating (5 h) at 60 °C, CMCase, -glucosidase, xylanase and -xylosidase retained 81.2, 86.8, 51.5 and 27.4% activity, respectively. 相似文献
76.
77.
The 1-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones were prepared via galactosidation of 3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide. The structure of the new galactosyl derivatives was based on both spectroscopic and chemical evidences. 相似文献
78.
Synthetic routes towards different 2-alpha-L-arabinopyranosyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-/ones or thiones were investigated. Primary human anticancer screening of two selected compounds resulted in an active compound against SF-268 (CNS) cell line. 相似文献
79.
Cao W Sohn UD Bitar KN Behar J Biancani P Harnett KM 《American journal of physiology. Gastrointestinal and liver physiology》2003,285(1):G86-G95
Esophageal (ESO) circular muscle contraction and lower esophageal sphincter (LES) tone are PKC dependent. Because MAPKs may be involved in PKC-dependent contraction, we examined ERK1/ERK2 and p38 MAPKs in ESO and LES. In permeabilized LES muscle cells, ERK1/2 antibodies reduced 1,2-dioctanoylglycerol (DG)- and threshold ACh-induced contraction, which are PKC dependent, but not maximal ACh, which is calmodulin dependent. LES tone was reduced by the ERK1/2 kinase inhibitor PD-98059 and by the p38 MAPK inhibitor SB-203580. In permeable ESO cells, ACh contraction was reduced by ERK1/ERK2 and p38 MAPK antibodies and by PD-98059 and SB-203580. ACh increased MAPK activity and phosphorylation of MAPK and of p38 MAPK. The 27-kDa heat shock protein (HSP27) antibodies reduced ACh contraction. HSP27 and p38 MAPK antibodies together caused no greater inhibition than either one alone. p38 MAPK and HSP27 coprecipitated after ACh stimulation, suggesting that HSP27 is linked to p38 MAPK. These data suggest that PKC-dependent contraction in ESO and LES is mediated by the following two distinct MAPK pathways: ERK1/2 and HSP27-linked p38 MAPK. 相似文献
80.