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Reduced Induction (reduced + induction)
Selected AbstractsGlycolipid-activated NKT cells support the induction of persistent plasma cell responses and antibody titersEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008Scott Devera Abstract NKT cell activation with CD1d-binding glycolipid ,-galactosylceramide (,-GC) enhances antibody responses to co-administered T-dependent antigen. The efficacy of ,-GC relative to other CD1d-binding glycolipids and adjuvants is not known. There is little information on how NKT cells affect antibody production beyond initial booster-stimulated recall responses. We therefore tested the hypothesis that ,-GC stimulates induction of plasma cells and antibody responses as effectively as Th1- and Th2-skewing variants of ,-GC and several other adjuvants. C57BL/6 and CD1d,/, mice were immunized with nitrophenol-conjugated keyhole limpet hemocyanin (NP-KLH) plus ,-GC or NP-KLH plus adjuvants before administration of an NP-KLH booster and assessing antibody responses and plasma cell frequency. ,-GC boosted long-term antibody responses as efficiently as all other agents tested and induced plasma cells that were detected in bone marrow 13,weeks after immunization. We then determined whether NKT cells were required in the presence of other adjuvants. CD1d,/, mice had a reduced induction of plasma cells in response to NP-KLH/Alum as compared to C57BL/6 mice. However, NKT cells were not required for the continued presence of those cells that were induced. Although NKT cells are capable of inducing persistent plasma cell responses, they may not play a major role in supporting longevity post-induction. [source] Doubly Truncated FosB Isoform (,2,FosB) Induces Osteosclerosis in Transgenic Mice and Modulates Expression and Phosphorylation of Smads in Osteoblasts Independent of Intrinsic AP-1 Activity,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008George Sabatakos Abstract Introduction: Activator protein (AP)-1 family members play important roles in the development and maintenance of the adult skeleton. Transgenic mice that overexpress the naturally occurring ,FosB splice variant of FosB develop severe osteosclerosis. Translation of ,fosb mRNA produces both ,FosB and a further truncated isoform (,2,FosB) that lacks known transactivation domains but, like ,FosB, induces increased expression of osteoblast marker genes. Materials and Methods: To test ,2,FosB's ability to induce bone formation in vivo, we generated transgenic mice that overexpress only ,2,FosB using the enolase 2 (ENO2) promoter-driven bitransgenic Tet-Off system. Results: Despite ,2,FosB's failure to induce transcription of an AP-1 reporter gene, the transgenic mice exhibited both the bone and the fat phenotypes seen in the ENO2-,FosB mice. Both ,FosB and ,2,FosB activated the BMP-responsive Xvent-luc reporter gene and increased Smad1 expression. ,2,FosB enhanced BMP-induced Smad1 phosphorylation and the translocation of phospho-Smad1 (pSmad1) to the nucleus more efficiently than ,FosB and showed a reduced induction of inhibitory Smad6 expression. Conclusions: ,FosB's AP-1 transactivating function is not needed to induce increased bone formation, and ,2,FosB may act, at least in part, by increasing Smad1 expression, phosphorylation, and translocation to the nucleus. [source] Diverse effects of Stat1 on the regulation of hsp90, gene under heat shock,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2007Xue-song Chen Abstract Stat1 has been known as a regulator of gene expression and a mediator of IFN, signaling in mammalian cells, while its effect in a heat shock response remains unclear. We used RNAi knockdown, point mutations, ChIP and promoter activity assays to study the effect of Stat1 on the heat-shock induction of the hsp90, gene under heat shock conditions. We found that Stat1 regulates the heat shock induction of its target genes, the hsp90, gene in a heat shock response while the constitutive activity of the gene remains unaffected. The result of Stat1 in complex with Stat3 and HSF1 that bound at the GAS to lead a moderate heat shock induction was designated as an "intrinsic" induction of the hsp90, gene. Additionally a reduced or an elevated level of heat shock induction was also controlled by the Stat1 on hsp90,. These diverse effects on the hsp90, gene were a "reduced" induction with over-expressed Stat1 elicited by transfection of wild-type Stat1 or IFN, treatment, bound at the GAS as homodimer; and an "enhanced" heat shock induction with a mutation-mediated prohibition of Stat1/GAS binding. In conclusion, the status and efficacy of Stat1 bound at the GAS of its target gene are pivotal in determining the impact of Stat1 under heat shock. The results provided the first evidence on the tumor suppressor Stat1 that it could play diverse roles on its target genes under heat shock that also shed lights on patients with fever or under thermotherapy. J. Cell. Biochem. 102: 1059,1066, 2007. © 2007 Wiley-Liss, Inc. [source] Multiple determinants influence root colonization and induction of induced systemic resistance by Pseudomonas chlororaphis O6MOLECULAR PLANT PATHOLOGY, Issue 6 2006SONG HEE HAN SUMMARY Colonization of the roots of tobacco by Pseudomonas chlororaphis O6 induces systemic resistance to the soft-rot pathogen, Erwinia carotovora ssp. carotovara SCC1. A screen of the transposon mutants of P. chlororaphis O6 showed mutants with about a fivefold reduction in ability to induce systemic resistance to the soft-rot disease. These mutations disrupted genes involved in diverse functions: a methyl-accepting chemotaxis protein, biosynthesis of purines, phospholipase C, transport of branched-chain amino acids and an ABC transporter. Additional mutations were detected in the intergenic spacer regions between genes encoding a GGDEF protein and fumarate dehydratase, and in genes of unknown function. The mutants in the ABC transporters did not display reduced root colonization. However, the other mutants had up to 100-fold reduced colonization levels. Generally the production of metabolites important for interactions in the rhizosphere, phenazines and siderophores, was not altered by the mutations. A reduced induction of systemic resistance by a purine biosynthesis mutant with a disrupted purM gene correlated with poor growth rate, lesser production of phenazines and siderophore and low levels of root colonization. These studies showed that multiple determinants are involved in the induction of systemic resistance, with there being a requirement for strong root colonization. [source] | |||||||||||||