bluuebunny/crossref_metadata_2025_split huggingface dataset:
High mobility group I/Y protein functions as a specific cofactor for Oct-2A: mapping of interaction domains
Authors: Abdulkadir Sarki A , Casolaro Vincenzo , Tai Albert K-F , Thanos Dimitris , Ono Santa Jeremy 
Published: January 2018

Abstract
The octamer motif (ATTTGCAT) present in several eukaryotic promoters and enhancers is now known to influence the transcription of several genes by interacting with members of a broad family of homeodomain proteins. The promoter of the human class II MHC gene HLA-DRA contains a conserved octamer element that can bind (among other proteins) the transcription factor Oct-2A and the high mobility group proteins (HMG) I/Y. We have previously determined that HMG I(Y) and Oct-2A cooperatively activate HLA-DRA gene expression, most likely due to the ability of HMG I(Y) to selectively recruit Oct-2A to the octamer motif. In this report, we present results of our investigations of the mechanisms of cooperative transactivation of HLA-DRA transcription by Oct-2A and HMG I(Y). We show that both the amino- and the carboxy-terminal domains of Oct-2A are required for HLA-DRA transacivation. Experiments using domain-swap chimeras of the Oct-1 and Oct-2A polypeptides indicate that cooperative activation of the DRA gene by HMG I(Y) and Oct-2A requires the carboxy-terminal domain (CTD) of Oct-2A. However, HMG I(Y) physically interacts with the conserved POU domains of both Oct-1 and Oct-2A. We therefore postulate that the nature of the CTD attached to the POU homeodomain influences the outcome of interaction with HMG I(Y). These studies support the view that HMG I(Y) is an important cofactor for HLA-DRA gene activation by Oct-2A and provide insights into its mechanism of action. J. Leukoc. Biol. 64: 681–691; 1998.
Murine leukocytes with ring-shaped nuclei include granulocytes, monocytes, and their precursors
Authors: Biermann Heike , Pietz Barbara , Dreier Rita , Schmid Kurt W , Sorg Clemens , Sunderkötter Cord 
Published: January 2018

Abstract
Leukocytes with ring-shaped nuclei (ring cells) are present in bone marrow (BM; ~50% of BM cells), in peripheral blood (PB), and in inflammatory infiltrates of mice, but also in humans during myeloproliferative disorders. They are usually referred to as polymorphonuclear cells (PMN), but we demonstrate that they additionally encompass different types of mononuclear (MNC)-like ring cells. PMN ring cells had constricted ring-shaped nuclei with a wide cytoplasmic center and were sorted among the GR-1high fraction. The MNC-like ring cells belonged to the GR-1low fraction. Their nuclei were not segmented and the cytoplasmic center of their nuclei was small. They were heterogeneous with one subgroup containing monocytes/macrophages according to ultrastructure, immunophenotype (BM8, F4/80, CD13, ER-HR3), activity of unspecific esterase, and phagocytosis of Leishmania major. A second subgroup contained myeloic precursor cells as they proliferated (Ki67), expressed ER-MP12, and showed on ultrastructure distribution patterns of peroxidase activity compatible with myelocytes, promyelocytes, or promonocytes. A third subgroup of cells had large, sometimes lobulated nuclei, was lineage markernegative/low (GR-1, Mac-1, B220 etc.), CD38−, but c-kit+ and sca-1+, and thus belonged to a close progeny of murine hematopoietic stem cells. In PB, ring cells encompassed mainly PMN, but also monocytes and cells with characteristics of both the granulocytic and monocytic lineage. Thus, ring cells comprise mature and precursor forms of myeloic cells. Their analysis revealed that in mice a clear distinction between the granulocytic and monocytic lineage beyond the GM-CFU stage is not always feasible. J. Leukoc. Biol. 65: 217–231; 1999.
Stimulus-specific regulation of chemokine expression involves differential activation of the redox-responsive transcription factors AP-1 and NF-κB
Authors: Roebuck Kenneth A , Carpenter Laura R , Lakshminarayanan Venkatesh , Page Scott M , Moy James N , Thomas Larry L 
Published: January 2018

Abstract
The promoters of the IL-8, MCP-1, and RANTES genes contain binding sites for the redox-responsive transcription factors AP-1 and NF-κB, which have been shown to be important for their expression. In this overview, we present evidence from our laboratories that the stimulus-specific regulation of these chemokines by the reactive oxidant H2O2, the proinflammatory cytokine TNF-α, and respiratory syncytial virus (RSV) is mediated in a cell type-specific manner involving different patterns of AP-1 and NF-κB binding activity. Our results demonstrate that H2O2 induction of IL-8 gene expression is linked with the selective binding of AP-1 to the IL-8 promoter, whereas TNF-α and RSV induction of IL-8 correlates with the activation of NF-κB binding. We propose that the differential activation and binding of inducible transcription factors to the promoter regions of chemokine genes provides a critical regulatory mechanism by which the CXC and CC chemokines can be selectively expressed in a cell type-specific and stimulus-specific manner. Such a regulatory mechanism of differential chemokine expression could critically influence the site- specific recruitment of distinct subsets of leukocytes to sites of inflammation and injury. J. Leukoc. Biol. 65: 291–298; 1999.
Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in acute and chronic inflammation
Authors: Connor Elaine M , Eppihimer Michael J , Morise Zenichi , Granger D Neil , Grisham Matthew B 
Published: January 2018

Abstract
The objective of this study was to quantify, in vivo, constitutive and tumor necrosis factor α (TNF-α)-enhanced expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in different tissues from healthy wild-type mice (C57BL/6) as well as interleukin-10 (IL-10)-deficient mice with and without active colitis. Using the dual radiolabel monoclonal antibody technique, we found substantial constitutive expression of MAdCAM-1 in the intestine, colon, and mesenteric lymph nodes. MAdCAM-1 expression in these tissues was significantly enhanced, in a time-dependent manner, by systemic administration of TNF-α. Maximum surface expression was observed at 18 h after TNF-α administration and remained significantly elevated at 48 h post-TNF-α injection. No significant constitutive nor TNF-α-induced expression of MAdCAM-1 was detected in skeletal muscle, brain, or heart. In IL-10-deficient (IL-10 k/o) mice with no clinical or histological evidence of colitis, constitutive and TNF-α-induced expression of MAdCAM-1 in the intestine, cecum, and colon was not different from those values obtained with healthy wild-type controls. IL-10-deficient mice with active colitis exhibited a four- to fivefold greater expression of MAdCAM-1 in the cecum and colon compared with their healthy controls or to IL-10 k/o mice with no evidence of colitis. Taken together, these data demonstrate that TNF-α enhances surface expression of MAdCAM-1 in intestinal and colonic tissues to the same extent in both wild-type and IL-10 k/o mice with no colonic inflammation, whereas IL-10 k/o mice with active colitis exhibited a profound up-regulation of MAd-CAM-1 in the colon. J. Leukoc. Biol. 65: 349–355; 1999.
Inflammation of the brain in Alzheimer's disease: implications for therapy
Authors: McGeer Patrick L , McGeer Edith G 
Published: January 2018

Abstract
We briefly describe the similarities and differences between a systemic and a local immune reaction and review the evidence that the latter occurs in Alzheimer's disease (AD) brains. The evidence comes mainly from studies on the complement system, microglia, and cytokines, all of which are important actors in the inflammatory process. The evidence is now overwhelming that the complement proteins and many of the mediators of inflammation are produced locally by brain cells. We will mention briefly the many epidemiological studies indicating that the use of anti-inflammatory drugs reduces the incidence and slows the progress of AD. Mention will also be made of some recent work on animal models of possible relevance to AD and inflammation. J. Leukoc. Biol. 65: 409–415; 1999.
Molecular pathway involved in HIV-1-induced CNS pathology: role of viral regulatory protein, Tat
Authors: Rappaport Jay , Joseph Jeymohan , Croul Sidney , Alexander Guillermo , Valle Luis Del , Amini Shohreh , Khalili Kamel 
Published: January 2018

Abstract
The broad range of histological lesions associated with HIV-1 are somewhat subtle relative to the clinical manifestations that occur as a result of HIV infection. Although it is clear that HIV has a causative role in CNS disease, dementia appears to be a consequence of the infiltration of inflammatory cells and cytokine dysregulation rather than the amount of virus in CNS. The HIV transregulatory protein Tat plays an important intracellular as well as extracellular role in the dysregulation of cytokines. The cytokines and possibly chemokines that are induced by Tat modify the action of astrocytes such that the survival of neurons is compromised. Pathogenetic alteration induced by Tat involves a series of interactions between circulating monocyte/macrophages, endothelial cells, and astrocytes. Cytokine dysregulation induced by viral infection and extracellular Tat leads to alterations in expression of adhesion molecules and promotes migration of non-infected inflammatory cells into the CNS compartment. We demonstrate here that recombinant HIV-1 Tat protein introduced by stereotaxic injection into mouse brain can induce pathologically relevant alterations including macrophage invasion as well as astrocytosis. The mechanism of destruction of the CNS by Tat appears to involve autocrine and paracrine pathways that depend not only on Tat, but cytokine and chemokine signaling pathways that are altered by viral infection. In this review, we discuss various pathogenic effects of Tat in brain cells and provide experimental evidence for an increased TNF-α level in CSF in mice injected intracerebrally with Tat protein. J. Leukoc. Biol. 65: 458–465; 1999.
Vitamin E protects against polymorphonuclear leukocyte-dependent adhesion to endothelial cells
Authors: Yoshida Norimasa , Yoshikawa Toshikazu , Manabe Hiroki , Terasawa Yoshimitsu , Kondo Motoharu , Noguchi Noriko , Niki Etsuo 
Published: January 2018

Abstract
We evaluated the effects of α-Toc on surface expression of CD11b/CD18 on polymorphonuclear leukocytes (PMN) stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and oxidized low-density lipoprotein (oxLDL). Incubation of PMN with fMLP (1 μM) or oxLDL (100 μg/mL) increased CD11b/CD18 expression; pretreatment with α-Toc reduced in a dose-dependent manner. PMN obtained from healthy adults ingesting 600 mg α-Toc per day for 10 days were similarly incubated with fMLP or oxLDL; the surface level of CD11b/CD18 was inversely correlated with serum α-Toc concentrations. Adherence of PMN to human umbilical vein endothelial cells was increased by fMLP or oxLDL stimulation but reduced by α-Toc pretreatment or anti-CD18 monoclonal antibodies. cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) activity in PMN was also assayed. A PKC inhibitor, but not a PKA inhibitor, suppressed CD11b/CD18 up-regulation, and α-Toc slightly decreased fMLP- and oxLDL-induced activation of PKC. These results suggest that α-Toc may prevent inflammation by both reducing CD11b/CD18 up-regulation and decreasing PMN-dependent adherence to EC. J. Leukoc. Biol. 65: 757–763; 1999.
Dendritic cells and MPIF-1: chemotactic activity and inhibition of endogenous chemokine production by IFN-γ and CD40 ligation
Authors: Nardelli Bernardetta , Morahan Diana K , Bong Gary W , Semenuk Mark A , Kreider Brent L , Garotta Gianni 
Published: January 2018

Abstract
We have examined the biological activity of the CC chemokine myeloid progenitor inhibitory factor 1 (MPIF-1) on human dendritic cells. MPIF-1 has chemotactic activity on dendritic cells derived from either peripheral blood monocytes or cord blood CD34+ progenitors. However, chemokine treatment did not induce further cell activation or maturation. In addition, MPIF-1 is constitutively released by monocyte-derived dendritic cells but not macrophages or monocytes (resting or stimulated). The proinflammatory stimuli lipopolysaccharide and tumor necrosis factor α, which induced the release of monocyte chemotactic protein-1, macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and interleukin-8, did not affect MPIF-1 release. In contrast, CD40 ligation and interferon-γ treatment, while stimulating the production of the other chemokines, caused a pronounced reduction of MPIF-1 transcript and protein release. Thus, in dendritic cells the regulation of the production and release of MPIF-1 is distinct in comparison to other CC and CXC chemokines. J. Leukoc. Biol. 65: 822–828; 1999.
Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin
Authors: Costelloe Elaine O , Stacey Katryn J , Antalis Toni M , Hume David A 
Published: January 2018

Abstract
We investigate the regulation of plasminogen activator inhibitor-2 (PAI-2) in murine macrophages. PAI-2 mRNA was inducible by bacterial lipopolysaccharide (LPS) in primary cells and macrophage-like cell lines. Evidence is presented for a role for autocrine factors, including cyclooxygenase products but not the cytokines tumor necrosis factor α or interferon-β (IFN-β). PAI-2 mRNA levels generally varied inversely from those of its target, urokinase-type plasminogen activator (uPA), and the macrophage growth factor CSF-1, which induces uPA, inhibited PAI-2 expression in cells treated subsequently with LPS. Expression of PAI-2 was distinct from that of other LPS-inducible genes in terms of induction time course, LPS dose response, and sensitivity to co-stimulation with IFN-γ. Induction of PAI-2 mRNA in subclones of the cell line RAW 264 was not uniform, reflecting heterogeneous expression in the parent line. The expression pattern of PAI-2 is discussed in terms of a possible role in LPS-induced pathology such as septicemia. J. Leukoc. Biol. 66: 172–182; 1999.
Suppression of cytokine-mediated β2-integrin activation on circulating neutrophils in critically ill patients
Authors: Rosenbloom Alan J , Pinsky Michael R , Napolitano Christopher , Nguyen Thu-Song , Levann Douglas , Pencosky Nicole , Dorrance Adrienne , Ray Barry K , Whiteside Theresa 
Published: January 2018

Abstract
The β2 integrin CD11b plays a central role in inflammation and the systemic inflammatory response syndrome (SIRS). The CD11b molecule activates in two ways: the density of membrane-bound CD11b up-regulates and the molecule undergoes a conformational change that confers adhesiveness to counter-receptors. We studied the kinetics of CD11b activation in patients with SIRS. We found a significantly diminished CD11b activation in response to tumor necrosis factor α (TNF-α). This affected all circulating polymorphonuclear neutrophils (PMN) and was an intrinsic property of the cells and not due to antagonism by soluble TNF-α receptors or loss of cellular receptors for TNF-α. Diminished responsiveness correlated with the severity of organ failure and lasted for months in some patients but had no impact on mortality. We speculate that reduced CD11b responsiveness in SIRS contributes to the high risk of recurrent infection, but that it may also be protective against excessive PMN activation within the vascular space. J. Leukoc. Biol. 65: 83–89; 1999.
Mechanisms of regulation of the MacMARCKS gene in macrophages by bacterial lipopolysaccharide
Authors: Chang Sandy , Stacey Katryn J , Chen Jianmin , Costelloe Elaine O , Aderem Alan , Hume David A 
Published: January 2018

Abstract
Bacterial lipopolysaccharide (LPS) stably induced the protein kinase C substrate, MacMARCKS, in murine resident peritoneal macrophages; initial induction of MacMARCKS mRNA was detected within 15 min and was protein synthesis-independent. This response was observed in the macrophage cell line RAW264, and occurred also in response to plasmid DNA, a partial mimetic of other responses to LPS. In murine bone marrow-derived macrophages, MacMARCKS was expressed constitutively due to induction by macrophage colony-stimulating factor. Nuclear run-on transcription revealed that, like tumor necrosis factor α (TNF-α), MacMARCKS was transcribed constitutively in RAW264 cells. The MacMARCKS promoter was sequenced to –1.7 kb and the transcription start site determined. Transient transfections of RAW264 cells revealed that the 113-bp GC-rich proximal promoter contained all the elements required for both high basal activity and 15- to 20-fold activation by LPS. J. Leukoc. Biol. 66: 528–534; 1999.
LPS-induced signals in activation of a caspase-3-like protease, a key enzyme regulating apoptotic cell damage into a macrophage-like cell line, J774.1, in the presence of cycloheximide
Authors: Karahashi Hisae , Amano Fumio 
Published: January 2018

Abstract
The earliest observed apoptotic change in a macrophage-like cell line, J774.1, treated with lipopolysaccharide (LPS) in the presence of cycloheximide (CHX) was a selective increase in caspase-3-like activity. The addition of polymyxin B, TPCK, herbimycin A, or genistein, all of which inhibited LPS-induced tumor necrosis factor α (TNF-α) production by macrophages, suppressed the activation of the caspase-3-like protease in these macrophages treated simultaneously with CHX. However, SB202190 and SB203580, inhibitors of MAP kinase, and PD98059, an inhibitor of MAP-kinase kinase (MEK), showed no effect on the activation of the caspase-3-like protease or on the cell damage of the macrophages treated with LPS and CHX, whereas they inhibited LPS-induced TNF-α production. These results suggest that some of the early signals in LPS-treated macrophages are common to the subsequent pathways for TNF-α production and caspase-3-like protease activation, but the later signals, like MAP-kinase kinase or MAP-kinase, are not involved in the pathways for caspase-3-like protease activation. J. Leukoc. Biol. 66: 689–696; 1999.
Nrampl: a link between intracellular iron transport and innate resistance to intracellular pathogens
Authors: Barton C Howard , Biggs Thelma E , Baker Stephen T , Bowen Holly , Atkinson Peter G P 
Published: January 2018

Abstract
Nramp1 (natural resistance-associated macrophage protein one) regulates intracellular pathogen proliferation and macrophage inflammatory responses. Murine Nramp1 exhibits a natural polymorphism with alleles termed resistant and susceptible. Alleles restrict or allow the proliferation of intracellular pathogens, respectively. Structural predictions suggest that Nramp1 encodes the prototypic member of a transporter family. Nramp1 exhibits sequence identity to Nramp2, which regulates intestinal and reticulocyte iron uptake. Based on this sequence identity we have initiated experiments for Nramp1 to investigate its role in macrophage iron homoeostasis and using a transfection approach in the RAW264.7 murine macrophagelike cell line, which lacks a functional Nramp1 gene. Nramp1 expression supports increased acute cytoplasmic influx of iron, detected using the fluorescent iron sensor dye calcein. Analysis of the endogenous iron sensors, iron regulatory protein 1 and 2, reveals a greater flux of iron in Nramp1-expressing cells and in its exclusion from the cytoplasm. Other work supports the prediction that Nramp1 is a phosphoprotein and the extent of phosphorylation changes in response to inflammatory cytokines. Together these data support the hypothesis that control of intracellular iron homoeostasis is a vital element used by phagocytes to control the proliferation of intracellular pathogens. J. Leukoc. Biol. 66: 757–762; 1999.
Down-regulation of the β-chemokine receptor CCR6 in dendritic cells mediated by TNF-α and IL-4
Authors: Carramolino Laura , Kremer Leonor , Goya íñigo , Varona Rosa , Buesa Jose María , Gutiérrez Julio , Zaballos Angel , Martínez-A. Carlos , Márquez Gabriel 
Published: January 2018

Abstract
Chemokines are involved in the control of dendritic cell (DC) trafficking, which is critical for the immune response. We have generated DC from human umbilical cord blood CD34+ progenitors cultured with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α (TNF-α), and stem cell factor. Using an anti-CCR6 monoclonal antibody, we observed that these cells showed maximum expression of this β-chemokine receptor when they were immature, as determined by their relatively low expression of several DC maturation markers such as CD1a, CD11c, CD14, CD40, CD80, and CD83. Immature DC responded strongly to macrophage inflammatory protein-3α (MIP-3α), the CCR6 ligand, in migration and calcium mobilization assays. CCR6 expression decreased in parallel with the DC maturation induced by prolonged TNF-α treatments. Interleukin-4 was also able to decrease CCR6 protein levels. Our findings suggest that the MIP-3α/CCR6 interaction plays an important role in the trafficking of immature DC to chemokine production sites such as injured or inflamed peripheral tissues, where DC undergo maturation on contact with antigens. J. Leukoc. Biol. 66: 837–844; 1999.
Nature versus nurture in T cell cytokine production
Authors: Fitzpatrick David R , Kelso Anne 
Published: January 2018

Abstract
Both extrinsic and intrinsic factors influence the development of cytokine expression patterns in T lymphocytes. The models proposed to accommodate these factors are often separated into two types: deterministic (or instructional) and probabilistic (or stochastic). In this review we compare these two types of models and examine how they account for different stages of T cell cytokine responses to antigen stimulation. We conclude by showing how a reconciliation of the two types of models may be possible, perhaps through the regulatory potential of heritable epigenetic mechanisms. This type of reconciliation may open up new avenues for manipulating T cell cytokine expression and redirecting immune responses. J. Leukoc. Biol. 66: 869–875; 1999.
Changes in susceptibility to Fas-mediated apoptosis during differentiation of HL-60 cells
Authors: Ohashi Masaru , Iwase Masayasu , Nagumo Masao 
Published: January 2018

Abstract
The Fas-mediated pathway has been implicated as an important cellular pathway mediating apoptosis in diverse cell types. We conducted studies to examine the susceptibility to Fas-mediated apoptosis of HL-60 cells treated with differentiation-inducing factors such as dimethyl sulfoxide (DMSO), retinoic acid (RA), and 1α, 25 dihydroxyvitamin D3 (VD3). Although the expression of Fas antigen (Ag) and its mRNA showed a marked increase in HL-60 cells with cell differentiation, that of Bcl-2 protein and its mRNA revealed the reverse. The expression of caspase proteins such as caspases-3 and -8 was also enhanced during cell differentiation. DNA fragmentation, annexin V binding, and caspase activities increased in differentiated HL-60 cells with the addition of anti-Fas Ag antibody. These findings were more clearly demonstrated in DMSO- or RA-induced neutrophil-like cells than in VD3-induced monocyte-like cells. Therefore, susceptibility to Fas-mediated apoptosis showed an increase with differentiation of HL-60 cells, especially in the neutrophil lineage. These results suggest that the difference of susceptibility to Fas-mediated apoptosis among cell populations depends on the expression of Fas Ag, Bcl-2, and caspases. Cell maturation and susceptibility to Fas-mediated apoptosis may be linked in hematopoietic cells. J. Leukoc. Biol. 67: 374–380; 2000.