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- Wang, HC, et al.
(författare)
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HMG-1 as a late mediator of endotoxin lethality in mice
- 1999
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 285:5425, s. 248-251
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Tidskriftsartikel (refereegranskat)abstract
- Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group–1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.
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| 5. |
- Zabel, B A, et al.
(författare)
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Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis
- 1999
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Ingår i: Journal of Experimental Medicine. - 1540-9538. ; 190:9, s. 1241-1256
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Tidskriftsartikel (refereegranskat)abstract
- TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein-coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti-GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory alpha4beta7(high) intestinal trafficking CD4 and CD8 lymphocytes. In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6. In contrast, GPR-9-6 is not displayed on cutaneous lymphocyte antigen-positive (CLA(+)) memory CD4 and CD8 lymphocytes, which traffic to skin inflammatory sites, or on other systemic alpha4beta7(-)CLA(-) memory CD4/CD8 lymphocytes. The majority of thymocytes also express GPR-9-6, but natural killer cells, monocytes, eosinophils, basophils, and neutrophils are GPR-9-6 negative. Transcripts of GPR-9-6 and TECK are present in both small intestine and thymus. Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes. As migration of these cells is blocked by anti-GPR-9-6 mAb 3C3, we conclude that GPR-9-6 is the principal chemokine receptor for TECK. In agreement with the nomenclature rules for chemokine receptors, we propose the designation CCR-9 for GPR-9-6. The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response.
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- Dever, Thomas E, et al.
(författare)
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Modulation of tRNA(iMet), eIF-2, and eIF-2B expression shows that GCN4 translation is inversely coupled to the level of eIF-2.GTP.Met-tRNA(iMet) ternary complexes
- 1995
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Ingår i: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 15:11, s. 6351-6363
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Tidskriftsartikel (refereegranskat)abstract
- To understand how phosphorylation of eukaryotic translation initiation factor (eIF)-2 alpha in Saccharomyces cerevisiae stimulates GCN4 mRNA translation while at the same time inhibiting general translation initiation, we examined the effects of altering the gene dosage of initiator tRNA(Met), eIF-2, and the guanine nucleotide exchange factor for eIF-2, eIF-2B. Overexpression of all three subunits of eIF-2 or all five subunits of eIF-2B suppressed the effects of eIF-2 alpha hyperphosphorylation on both GCN4-specific and general translation initiation. Consistent with eIF-2 functioning in translation as part of a ternary complex composed of eIF-2, GTP, and Met-tRNA(iMet), reduced gene dosage of initiator tRNA(Met) mimicked phosphorylation of eIF-2 alpha and stimulated GCN4 translation. In addition, overexpression of a combination of eIF-2 and tRNA(iMet) suppressed the growth-inhibitory effects of eIF-2 hyperphosphorylation more effectively than an increase in the level of either component of the ternary complex alone. These results provide in vivo evidence that phosphorylation of eIF-2 alpha reduces the activities of both eIF-2 and eIF-2B and that the eIF-2.GTP. Met-tRNA(iMet) ternary complex is the principal component limiting translation in cells when eIF-2 alpha is phosphorylated on serine 51. Analysis of eIF-2 alpha phosphorylation in the eIF-2-overexpressing strain also provides in vivo evidence that phosphorylated eIF-2 acts as a competitive inhibitor of eIF-2B rather than forming an excessively stable inactive complex. Finally, our results demonstrate that the concentration of eIF-2-GTP. Met-tRNA(iMet) ternary complexes is the cardinal parameter determining the site of reinitiation on GCN4 mRNA and support the idea that reinitiation at GCN4 is inversely related to the concentration of ternary complexes in the cell.
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| 8. |
- Heinzel, T., et al.
(författare)
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A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression
- 1997
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 387:6628, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional repression by nuclear receptors has been correlated to binding of the putative co-repressor, N-CoR. A complex has been identified that contains N-CoR, the Mad presumptive co-repressor mSin3, and the histone deacetylase mRPD3, and which is required for both nuclear receptor- and Mad-dependent repression, but not for repression by transcription factors of the ets-domain family. These data predict that the ligand-induced switch of heterodimeric nuclear receptors from repressor to activator functions involves the exchange of complexes containing histone deacetylases with those that have histone acetylase activity.
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- Magnuson, Martin, et al.
(författare)
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Competition between decay and dissociation of core-excited carbonyl sulfide studied by x-ray scattering
- 1999
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 59:6, s. 4281-4287
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Tidskriftsartikel (refereegranskat)abstract
- We show evidence of dissociation during resonant inelastic soft x-ray scattering Carbon and oxygen K-shell and sulfur L-shell resonant and nonresonant x-ray emission spectra were measured using monochromatic synchrotron radiation for excitation and ionization. After sulfur L-2,L-3-->pi*, sigma* excitation, atomic lines are observed in the emission spectra as a consequence of competition between de-excitation and dissociation. In contrast thr carbon and oxygen spectra show weaker line-shape variations and no atomic Lines. The spectra are compared to results from ab initio calculations. The discussion of the dissociation paths is based on calculated potential energy surfaces and atomic transition energies.
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| 10. |
- Magnuson, Martin, 1965-, et al.
(författare)
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Resonant inelastic soft X-ray scattering spectra at the nitrogen and carbon K-edges of poly(pyridine-2,5-diyl)
- 1999
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - 0368-2048 .- 1873-2526. ; 101-103, s. 573-578
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Tidskriftsartikel (refereegranskat)abstract
- Resonant inelastic scattering measurements of the conjugated polymer, poly(pyridine-2,5-diyl) have been performed at the nitrogen and carbon K-edges using synchrotron radiation. For comparison, molecular orbital calculations of the spectra have been carried out with the repeat unit as a model molecule of the polymer chain. The resonant emission spectra show depletion of the π electron bands which is consistent with symmetry selection and momentum conservation rules. The depletion is most obvious in the resonant inelastic scattering spectra of carbon while the nitrogen spectra are dominated by lone pair n orbital emission of σ symmetry and are less excitation energy dependent. By comparing the measurements to calculations an isomeric dependence of the resonant spectra is found giving preference to two of the four possible isomers in the polymer.
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