Selective blockade of NF-kappa B by novel mutated I kappa B alpha suppresses CD3/CD28-induced activation of memory CD4(+) T cells in asthma

Background:Nuclear factor kappa B(NF-kappa B) overactivation plays a crucial role in T-helper 2 (Th2)-biased allergic airway inflammation by increased activation and decreased apoptosis of CD4(+) T cells. We have shown that targeted NF-kappa B suppression in dendritic cells by adenoviral gene transfer of a novel mutated inhibitor of NF-kappa B(I kappa B alpha) (AdI kappa B alpha M) contributes to T-cell tolerance, but the immunosuppressive action of AdI kappa B alpha M on memory(CD45RO(+)) CD4(+) T cells remains enigmatic. Methods:CD45RO(+) T cells from Dermatophagoides farinaei-sensitized asthmatic patients, untransfected or transfected with AdI kappa B alpha M or AdLacZ(beta-galactosidase) for 24 h, were stimulated with anti-CD3(1.0 mu g/ml) plus anti-CD28(0.5 mu g/ml) monoclonal antibody for an additional 24 h. I kappa B alpha M transgene expression and NF-kappa B activation were detected by polymerase chain reaction(PCR), reverse transcription-PCR(RT-PCR), Western blot analysis, and electrophoretic mobility shift assay. Phenotype and apoptosis were measured by flow cytometry, annexin V binding, and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling analyses. Cytokine production and cell proliferation were determined using enzyme-linked immunosorbent assay andH-3 thymidine incorporation. Results:A unique 801-bp I kappa B alpha M cDNA and a dose-dependent increase in I kappa B alpha M transgene expression were observed in AdI kappa B alpha M-transfected CD45RO(+) T cells. Significantly, AdI kappa B alpha M inhibited CD3/CD28-mediated NF-kappa B activation in CD45RO(+) T cells, leading to evident apoptosis, reduction of eotaxin, RANTES, Th1 interferon (IFN)-gamma and interleukin (IL)-2, and Th2 (IL-4, IL-5, and IL-13 despite a slight decrease in IL-10) cytokines and secondary proliferative response. AdI kappa B alpha M also upregulated cytotoxic T lymphocyte-associated antigen 4(CTLA-4) and downregulated CD69 besides no change in CD28. Conclusion:I kappa B alpha M might be beneficial to augment memory CD4(+) T-cell tolerance through modulating B7-CD28/CTLA-4 co-stimulatory pathways and NF-kappa B-dependent cytokine profiles in allergic inflammatory diseases including asthma.

Recent Advances on Non-Marine Late Paleozoic Strata and Floras： Outcome of the 16th International Congress on the Carboniferous and Permian

The 16th International Congress on the Carboniferous and Permian （ICCP XVI） orga- nized by the Nanjing Institute of Geology and Palaeontology under the Chinese Acad- emy of Sciences, the Institute of Geology under the Chinese Academy of Geological Sciences, the China University of Geo- sciences and the Nanjing University took place in Nanjing, June 21-24, 2007. More than 150 colleagues from over 20 countries attended the quadrennial conference.

Nature：大规模研究揭示生命所必需的基因

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期刊上，论文标题为“High—throughput discovery of novel developmental phenotypes”。