bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation and Characterization of a Novel IgD-Binding Protein fromMoraxella catarrhalis
Authors: Forsgren Arne , Brant Marta , Möllenkvist Andrea , Muyombwe Anthony , Janson Håkan , Woin Nicolas , Riesbeck Kristian 
Published: April 2014

AbstractA novel surface protein of the bacterial species Moraxella catarrhalis that displays a high affinity for IgD (MID) was solubilized in Empigen and isolated by ion exchange chromatography and gel filtration. The apparent molecular mass of monomeric MID was estimated to ∼200 kDa by SDS-PAGE. The mid gene was cloned and expressed in Escherichia coli. The complete mid nucleotide gene sequence was determined, and the deduced amino acid sequence consists of 2123 residues. The sequence of MID has no similarity to other Ig-binding proteins and differs from all previously described outer membrane proteins of M. catarrhalis. MID was found to exhibit unique Ig-binding properties. Thus, in ELISA, dot blots, and Western blots, MID bound two purified IgD myeloma proteins, four IgD myeloma sera, and finally one IgD standard serum. No binding of MID was detected to IgG, IgM, IgA, or IgE myeloma proteins. MID also bound to the surface-expressed B cell receptor IgD, but not to other membrane molecules on human PBLs. This novel Ig-binding reagent promises to be of theoretical and practical interest in immunological research.
E2A and HEB Activate the Pre-TCRα Promoter During Immature T Cell Development
Authors: Takeuchi Arata , Yamasaki Sho , Takase Kan , Nakatsu Fubito , Arase Hisashi , Onodera Makoto , Saito Takashi 
Published: April 2014

Abstract
The pre-TCRα (pTα) is exclusively expressed in immature thymocytes and constitutes the pre-TCR complex with TCRβ, which regulates early T cell differentiation. Despite the recent identification of the pTα enhancer, the contribution of the promoter region, the direct DNA-protein interaction, and the regulation of such interaction along with T cell development have not been investigated. We analyzed the pTα promoter region and identified the critical elements for transcription of the pTα gene. The pTα promoter was found to contain two consecutive E-box elements that are critical for pTα transcription. The E-box elements in the promoter region formed the specific DNA-protein complex that was exclusively observed in immature thymocytes, not in mature thymocytes and T cells. The E proteins in this complex were identified as E2A and HeLa E-box binding protein (HEB), and overexpression of E2A and HEB resulted in activation of the pTα promoter. The binding complex in the consecutive E-boxes in the pTα promoter changed along with T cell development, as a distinct DNA-binding complex was observed in mature T cells. Comparing the E-box regions in the enhancer and the promoter, those in the promoter appear to make a greater contribution to pTα gene transcription.
Mycobacterial Lysocardiolipin Is Exported from Phagosomes upon Cleavage of Cardiolipin by a Macrophage-Derived Lysosomal Phospholipase A2
Authors: Fischer Karsten , Chatterjee Delphi , Torrelles Jordi , Brennan Patrick J. , Kaufmann Stefan H. E. , Schaible Ulrich E. 
Published: April 2014

Abstract
Pathogenic mycobacteria are able to survive and proliferate in phagosomes within host macrophages (Mφ). This capability has been attributed in part to their cell wall, which consists of various unique lipids. Some of these are important in the host-pathogen interaction, such as resistance against microbicidal effector mechanisms and modulation of host cell functions, and/or are presented as Ags to T cells. Here we show that two lipids are released from the mycobacterial cell wall within the phagosome of infected Mφ and transported out of this compartment into intracellular vesicles. One of these lipids was identified as lysocardiolipin. Lysocardiolipin was generated through cleavage of mycobacterial cardiolipin by a Ca2+-independent phospholipase A2 present in Mφ lysosomes. This result indicates that lysosomal host cell enzymes can interact with released mycobacterial lipids to generate new products with a different intracellular distribution. This represents a novel pathway for the modification of bacterial lipid Ags.
Toxoplasma gondiiTachyzoites Inhibit Proinflammatory Cytokine Induction in Infected Macrophages by Preventing Nuclear Translocation of the Transcription Factor NF-κB
Authors: Butcher Barbara A. , Kim Leesun , Johnson Peter F. , Denkers Eric Y. 
Published: April 2014

AbstractControl of microbial infection requires regulated induction of NF-κB-dependent proinflammatory cytokines such as IL-12 and TNF-α. Activation of this important transcription factor is driven by phosphorylation-dependent degradation of the inhibitory IκB molecule, an event which enables NF-κB translocation from the cytoplasm to the nucleus. In this study, we show that intracellular infection of macrophages with the protozoan parasite Toxoplasma gondii induces rapid IκB phosphorylation and degradation. Nevertheless, NF-κB failed to translocate to the nucleus, enabling the parasite to invade cells without triggering proinflammatory cytokine induction. Infected cells subsequently subjected to LPS triggering were severely crippled in IL-12 and TNF-α production, a result of tachyzoite-induced blockade of NF-κB nuclear translocation. Our results are the first to demonstrate the ability of an intracellular protozoan to actively interfere with the NF-κB activation pathway in macrophages, an activity that may enable parasite survival within the host.
Protective Roles of Mast Cells Against Enterobacterial Infection Are Mediated by Toll-Like Receptor 4
Authors: Supajatura Volaluck , Ushio Hiroko , Nakao Atsuhito , Okumura Ko , Ra Chisei , Ogawa Hideoki 
Published: April 2014

Abstract
Toll-like receptors (TLRs) are mammalian homologues of the Drosophila Toll receptors and are thought to have roles in innate recognition of bacteria. We demonstrated that TLR 2, 4, 6, and 8 but not TLR5 were expressed on mouse bone marrow-derived mast cells (BMMCs). Using BMMCs from the genetically TLR4-mutated strain C3H/HeJ, we demonstrated that functional TLR4 was required for a full responsiveness of BMMCs to produce inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-13) by LPS stimulation. TLR4-mediated stimulation of mast cells by LPS was followed by activation of NF-κB but not by stress-activated protein kinase/c-Jun NH2-terminal kinase signaling. In addition, in the cecal ligation and puncture-induced acute septic peritonitis model, we demonstrated that genetically mast cell-deficient W/Wv mice that were reconstituted with TLR4-mutated BMMCs had significantly higher mortality than W/Wv mice reconstituted with TLR4-intact BMMCs. Higher mortality of TLR4-mutated BMMC-reconstituted W/Wv mice was well correlated with defective neutrophil recruitment and production of proinflammatory cytokines in the peritoneal cavity. Taken together, these observations provide definitive evidence that mast cells play important roles in exerting the innate immunity by releasing inflammatory cytokines and recruitment of neutrophils after recognition of enterobacteria through TLR4 on mast cells.
Taurine Chloramine Inhibits Inducible Nitric Oxide Synthase and TNF-α Gene Expression in Activated Alveolar Macrophages: Decreased NF-κB Activation and IκB Kinase Activity
Authors: Barua Madhabi , Liu Yong , Quinn Michael R. 
Published: April 2014

Abstract
Taurine prevents tissue damage in a variety of models that involve inflammation, including oxidant-induced lung damage. The mechanism of protection is uncertain, but is postulated to involve the actions of taurine chloramine (Tau-Cl) derived via halide-dependent myeloperoxidase associated with neutrophils. Understanding the influence of Tau-Cl on the production of inflammatory mediators by alveolar macrophages provides an opportunity for determining the mechanism of Tau-Cl action. The effects of Tau-Cl were evaluated on the production of NO and TNF-α in NR8383, a cloned cell line derived from rat alveolar macrophages (RAM), and in primary cultures of RAM. Production of NO and TNF-α, and expression of inducible NO synthase was inhibited by Tau-Cl in activated NR8383 cells as well as in RAM. Temporal (2, 4, 8, 24 h) expression of inducible NO synthase and TNF-α mRNAs was reduced by Tau-Cl in NR8383 cells. Tau-Cl depressed NF-κB migration into the nucleus of activated NR8383 cells and caused a more sustained presence of IκB in the cytoplasm. Stabilization of cytoplasmic IκB-α in Tau-Cl-treated cells resulted from decreased phosphorylation of IκB-α serine-32 and a lower activity of IκB kinase (IKK). Additional experiments demonstrated that Tau-Cl does not directly inhibit IKK activity. These results suggest that Tau-Cl exerts its effects at some level upstream of IKK in the signaling pathway and inhibits production of inflammatory mediators through a mechanism that, at least in part, involves inhibition of NF-κB activation.
A Critical Role for Mouse CXC Chemokine(s) in Pulmonary Neutrophilia During Th Type 1-Dependent Airway Inflammation
Authors: Takaoka Akiko , Tanaka Yoshitaka , Tsuji Takemasa , Jinushi Takafumi , Hoshino Akihiko , Asakura Yumiko , Mita Yasuo , Watanabe Kazuhito , Nakaike Shiro , Togashi Yuji , Koda Toshiaki , Matsushima Kouji , Nishimura Takashi 
Published: April 2014

Abstract
Ag-specific Th1 and Th2 cells have been demonstrated to play a critical role in the induction of allergic diseases. Here we have investigated the precise mechanisms of Th1-induced airway inflammation. Airway inflammation was induced in BALB/c mice by transfer of freshly induced OVA-specific Th1 or Th2 cells followed by OVA inhalation. In this model, both Th1 and Th2 cells induced airway inflammation. The former induced neutrophilia in airways, whereas the latter induced eosinophilia. Moreover, we found that Th1 cells induced more severe airway hyperresponsiveness (AHR) than Th2 cells. The eosinophilia induced by Th2 cell infusion was almost completely blocked by administration of anti-IL-5 mAb, but not anti-IL-4 mAb. In contrast, Th1-induced AHR and pulmonary neutrophilia were inhibited by the administration of anti-human IL-8R Ab, which blocks the function of mouse CXC chemokine(s). These findings reveal a critical role of mouse CXC chemokine(s) in Th1-dependent pulmonary neutrophilia and AHR.
Increased Frequency of Pre-germinal Center B Cells and Plasma Cell Precursors in the Blood of Children with Systemic Lupus Erythematosus
Authors: Arce Edsel , Jackson Deborah G. , Gill Michelle A. , Bennett Lynda B. , Banchereau Jacques , Pascual Virginia 
Published: April 2014

AbstractWe have analyzed the blood B cell subpopulations of children with systemic lupus erythematosus (SLE) and healthy controls. We found that the normal recirculating mature B cell pool is composed of four subsets: conventional naive and memory B cells, a novel B cell subset with pregerminal center phenotype (IgD+CD38+centerin+), and a plasma cell precursor subset (CD20−CD19+/lowCD27+/++ CD38++). In SLE patients, naive and memory B cells (CD20+CD38−) are ∼90% reduced, whereas oligoclonal plasma cell precursors are 3-fold expanded, independently of disease activity and modality of therapy. Pregerminal center cells in SLE are decreased to a lesser extent than conventional B cells, and therefore represent the predominant blood B cell subset in a number of patients. Thus, SLE is associated with major blood B cell subset alterations.
Cutting Edge: Identification of a Hybrid Cytokine Consisting of IL-7 and the β-Chain of the Hepatocyte Growth Factor/Scatter Factor
Authors: Lai Laijun , Goldschneider Irving 
Published: April 2014

Abstract
Pre-pro-B cell growth-stimulating factor (PPBSF) is a heterodimer of IL-7 and a 30-kDa cofactor. Unlike monomeric IL-7, PPBSF selectively induces proliferation and differentiation of pre-pro-B cells and up-regulates IL-7Rα-chain expression. Here we clone the PPBSF cofactor from bone marrow stromal cells and identify it as a variant β-chain of hepatocyte growth factor (HGF), a pleiotropic cytokine homologous to plasminogen that regulates cell growth, motility, and morphogenesis. We further demonstrate that, in the presence of low m.w. heparin sulfate-derived oligosaccharides, rHGFβ combines with rIL-7 to form a biologically active heterodimer having the properties of PPBSF. The results indicate that PPBSF is a novel form of cytokine (hybrid cytokine) consisting of the bioactive components of two unrelated cytokines. Based on its heparin-binding and mitogenic properties, we postulate that the HGFβ-chain in PPBSF enables IL-7 to participate in cognate interactions at the stromal cell surface and to transduce signals effectively at low levels of IL-7R.
Cutting Edge: Role of Toll-Like Receptor 9 in CpG DNA-Induced Activation of Human Cells
Authors: Takeshita Fumihiko , Leifer Cynthia A. , Gursel Ihsan , Ishii Ken J. , Takeshita Saoko , Gursel Mayda , Klinman Dennis M. 
Published: April 2014

Abstract
Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines and PBMC that recognize CpG DNA express membrane-bound human Toll-like receptor 9 (hTLR9). Cells that are not responsive to CpG DNA become responsive when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake of CpG (but not control) DNA into endocytic vesicles. Upon cell stimulation, hTLR9 and CpG DNA are found in the same endocytic vesicles. Cells expressing hTLR9 are stimulated by CpG motifs that are active in primates but not rodents, suggesting that evolutionary divergence between TLR9 molecules underlies species-specific differences in the recognition of bacterial DNA. These findings indicate that hTLR9 plays a critical role in the CpG DNA-mediated activation of human cells.
Tumoricidal Activity of Monocyte-Derived Dendritic Cells: Evidence for a Caspase-8-Dependent, Fas-Associated Death Domain-Independent Mechanism
Authors: Vanderheyde Nathalie , Aksoy Ezra , Amraoui Zoulikha , Vandenabeele Peter , Goldman Michel , Willems Fabienne 
Published: April 2014

Abstract
Monocyte-derived dendritic cells (DC) were found to be cytotoxic for several tumor cell lines including Jurkat cells, which were killed through a calcium-independent pathway. K562 cells were resistant, excluding a NK cell-like activity. DC-mediated apoptosis did not involve classical death receptors because it was not reversed by blocking TNF/TNFR, CD95/CD95 ligand, or TNF-related apoptosis-inducing ligand/TNF-related apoptosis-inducing ligand receptor interactions. Fas-associated death domain-deficient, but not caspase-8 deficient, Jurkat cells were killed by DC. Indeed, caspase-8 cleavage was demonstrated in Jurkat cells cocultured with DC, and the use of specific caspase inhibitors confirmed that apoptosis triggered by DC was caspase-8 dependent. Furthermore, the involvement of Bcl-2 family members in the control of DC-mediated apoptosis was demonstrated by Bid cleavage in Jurkat cells cocultured with DC and resistance of Jurkat cells overexpressing Bcl-2 to DC-mediated cytotoxicity. Overall, these data indicate that monocyte-derived DC exert a caspase-8-dependent, Fas associated death domain-independent tumoricidal activity, a finding that could be relevant to their therapeutic use in cancer.
An Atypical Population of NK Cells That Spontaneously Secrete IFN-γ and IL-4 Is Present in the Intraepithelial Lymphoid Compartment of the Rat
Authors: Todd Derrick J. , Greiner Dale L. , Rossini Aldo A. , Mordes John P. , Bortell Rita 
Published: April 2014

Abstract
The intestinal lymphoid compartment of the rat is large and diverse, but the phenotype and functions of its constituent cell populations are not fully characterized. Using new methodology for the isolation and purification of rat intestinal intraepithelial lymphocytes (IELs), we previously identified a population of αβ- and γδ-TCR− NKR-P1A+ NK cells. These cells were almost completely restricted to the CD4−CD8− IEL population, and unlike peripheral NK cells in the rat, they were CD2−. We now report that rat intraepithelial NK (IENK) and peripheral NK cells are similar in morphology, in their ability to lyse NK-sensitive targets, and in their ability to suppress a one-way mixed lymphocyte culture. In contrast, however, intraepithelial and splenic NK cells differ markedly in two respects. First, IENK cells express high levels of ADP-ribosyltransferase 2 (a marker of regulatory T cells in the rat) and CD25, whereas peripheral NK cells do not. Second, unlike splenic NK cells, a substantial fraction of IENK cells appear to spontaneously secrete IL-4 and/or IFN-γ. We conclude that the rat IEL compartment harbors a large population of NKR-P1A+CD3− cells that function as NK cells but display an activated phenotype and unusual cytokine profile that clearly distinguish them from splenic NK cells. Their phenotypic and functional characteristics suggest that these distinctive IENK cells may participate in the regulation of mucosal immunity.
Bm1–Bm5 Classification of Peripheral Blood B Cells Reveals Circulating Germinal Center Founder Cells in Healthy Individuals and Disturbance in the B Cell Subpopulations in Patients with Primary Sjögren’s Syndrome
Authors: Bohnhorst Janne Ø. , Bjørgan Marie B. , Thoen Jørn E. , Natvig Jacob B. , Thompson Keith M. 
Published: April 2014

AbstractAnalyses of B cells in the bone marrow and secondary lymphoid tissues have revealed a broad range of cell surface markers defining B cell subpopulations, but only a few of these have been used to analyze B cell subpopulations in peripheral blood (PB). We report here the delineation of circulating PB B cell subpopulations by staining for CD19, CD38, and IgD in combination with CD10, CD44, CD77, CD95, CD23, IgM, and the B cell memory marker CD27. The utility of this approach is shown by the demonstration of disturbances of circulating B cell subpopulations in patients with autoimmune disease. Five mature B cell (Bm) subpopulations were identified in normal PB that were comparable with the tonsillar Bm1, Bm2, early Bm5, Bm5 subpopulations and, surprisingly, to the germinal center (GC) founder cell subpopulation (Bm2′ and Bm3δ–4δ), suggesting that some GC founder cells are circulating. No PB B cells resembled the Bm3 and Bm4 GC cells. Remarkably, some cells with the CD38−IgD+ phenotype, previously known as naive Bm1 cells, expressed CD27. The CD38−IgD+ subpopulation therefore includes both naive Bm1 cells and IgD+ memory B cells. This new classification of B cell developmental stages reveals disturbances in the proportions of B cell subpopulations in primary Sjögren’s syndrome (pSS) patients compared with healthy donors and rheumatoid arthritis patients. Patients with pSS contained a significantly higher percentage of B cells in two activated stages, which might reflect a disturbance in B cell trafficking and/or alteration in B cell differentiation. These findings could be of diagnostic significance for pSS.
IL-10 Inhibits Granulocyte-Macrophage Colony-Stimulating Factor-Dependent Human Monocyte Survival at the Early Stage of the Culture and Inhibits the Generation of Macrophages
Authors: Hashimoto Shin-ichi , Komuro Iwao , Yamada Muneo , Akagawa Kiyoko S. 
Published: April 2014

Abstract
We previously demonstrated that IL-10 alone does not stimulate growth and differentiation of human monocytes, but enhances those of monocytes stimulated with M-CSF. We studied here the effect of IL-10 on human monocytes stimulated with GM-CSF. Monocytes stimulated with GM-CSF alone survived and developed into macrophages. Monocytes cultured with GM-CSF plus IL-10, however, died through apoptosis. IL-10 decreased expression of bcl-2, bcl-xL, and mcl-1- but not bax mRNA in monocytes stimulated with GM-CSF. IL-10 did not change the expression of mRNA of both GM-CSFR α-chain and β-chain, but inhibited tyrosine phosphorylation of STAT5 and extracellular signal-regulated kinases 1 and 2 in the monocytes. The inhibitory effect of IL-10 was restricted to treatment 48 h after stimulation with GM-CSF. Addition of IL-10 after that time induced neither apoptosis nor a decrease in expression of bcl-2, bcl-xL, and mcl-1 mRNA. IL-10, however, inhibited LPS-induced TNF-α production even in these cells, indicating that the cells still possessed responsiveness to IL-10. Monocytes pretreated for &gt;48 h with GM-CSF became resistant to GM-CSF withdrawal, and the cells could survive without GM-CSF. These results indicate that IL-10 selectively inhibits GM-CSF-dependent monocyte survival by inhibiting the signaling events induced by GM-CSF, but the timing of addition of IL-10 is critical, and IL-10 had to be added within 48 h after stimulation with GM-CSF to achieve the inhibitory effect. These results taken together with our previous results indicate that IL-10 plays a pivotal role in monocyte survival and development into macrophages in concert with M-CSF and GM-CSF.
Mechanisms of Nuclear Import and Export That Control the Subcellular Localization of Class II Transactivator
Authors: Cressman Drew E. , O’Connor William J. , Greer Susanna F. , Zhu Xin-Sheng , Ting Jenny P.-Y. 
Published: April 2014

Abstract
The presence of the class II transactivator (CIITA) activates the transcription of all MHC class II genes. Previously, we reported that deletion of a carboxyl-terminal nuclear localization signal (NLS) results in the cytoplasmic localization of CIITA and one form of the type II bare lymphocyte syndrome. However, further sequential carboxyl-terminal deletions of CIITA resulted in mutant forms of the protein that localized predominantly to the nucleus, suggesting the presence of one or more additional NLS in the remaining sequence. We identified a 10-aa motif at residues 405–414 of CIITA that contains strong residue similarity to the classical SV40 NLS. Deletion of this region results in cytoplasmic localization of CIITA and loss of transactivation activity, both of which can be rescued by replacement with the SV40 NLS. Fusion of this sequence to a heterologous protein results in its nuclear translocation, confirming the identification of a NLS. In addition to nuclear localization sequences, CIITA is also controlled by nuclear export. Leptomycin B, an inhibitor of export, blocked the nuclear to cytoplasmic translocation of CIITA; however, leptomycin did not alter the localization of the NLS mutant, indicating that this region mediates only the rate of import and does not affect CIITA export. Several candidate nuclear export sequences were also found in CIITA and one affected the export of a heterologous protein. In summary, we have demonstrated that CIITA localization is balanced between the cytoplasm and nucleus due to the presence of NLS and nuclear export signal sequences in the CIITA protein.