bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-transcriptional regulation of TNF-α during in vitro differentiation of human monocytes/macrophages in primary culture
Authors: MacKenzie Simon , Fernàndez-Troy Neus , Espel Enric 
Published: September 2022

AbstractTumor necrosis factor α (TNF-α), a proinflammatory cytokine, is produced abundantly by monocytes and macrophages. We have compared LPS-stimulated TNF-α production and regulation in freshly isolated human monocytes and macrophages differentiated in vitro. A significant increase in LPS-induced TNF-α protein secretion was observed in macrophages over freshly isolated monocytes without comparable differences in TNF-α mRNA induction. Polysome gradient analysis showed polysome-mRNA distribution did not change, whereas TNF-α mRNA stability increased in macrophages. Tristetraprolin mRNA expression was constitutive and decreased with differentiation-linked kinetics. Blockable LPS-inducible MAP kinase activity (p38, ERK) affected TNF-α biosynthesis differentially at the transcriptional and post-transcriptional level throughout the culture period. We suggest that the increase in TNF-α secretion in macrophages relates to changes in post-transcriptional processing, which is regulated indirectly by the expression of RNA-binding proteins. Changes in gene expression throughout monocytic differentiation equip the cell to act as a more potent producer of this proinflammatory cytokine.
Eicosapentaenoic acid inhibits CSF-induced human monocyte survival and maturation into macrophage through the stimulation of H2O2 production
Authors: Terada Sachiyo , Takizawa Mari , Yamamoto Shigeru , Ezaki Osamu , Itakura Hiroshige , Akagawa Kiyoko S 
Published: September 2022

AbstractHuman studies suggest a beneficial effect of eicosapentaenoic acid (EPA)-supplemented diets on atherosclerotic and atherothrombotic disorders as well as autoimmune and inflammatory diseases and tumors. The effects of EPA on human monocyte survival and maturation into macrophage are not yet known. We studied the effects of EPA on the survival and development into macrophage of human monocyte treated with colony-stimulating factor (CSF). We have found that EPA induces cell death of the monocyte via apoptosis, even in the presence of M-CSF or GM-CSF, and inhibits differentiation from the monocyte to macrophage by inducing H2O2 production. In contrast to the effect of EPA on monocytes, EPA did not induce cell death of monocyte-derived macrophages. Such an apoptosis inducing effect on monocytes by EPA may contribute to the efficacy of EPA in atherosclerosis and autoimmune diseases.
Sorting of neutrophil-specific granule protein human cathelicidin, hCAP-18, when constitutively expressed in myeloid cells
Authors: Bülow Elinor , Bengtsson Niklas , Calafat Jero , Gullberg Urban , Olsson Inge 
Published: September 2022

AbstractNeutrophil granulocytes carry storage organelles, e.g., azurophil and specific granules. Poorly understood are the mechanisms for retrieval from constitutive secretion followed by sorting for storage. Therefore, we asked whether the specific granule protein human cathelicidin (hCAP-18) could be sorted for storage in other granules when the biosynthetic window is widened to allow this. We observed that hCAP-18 was targeted for storage in lysosome-related organelles when expressed constitutively in the rat basophilic leukemia and the mouse promyelocytic (MPRO) cell lines. In addition, premature release of the antibiotic C-terminal peptide LL-37 was observed. Retention of hCAP-18 was diminished by induction of differentiation of MPRO cells. In conclusion, a specific granule protein with native conformation may be sorted for storage in lysosome-related organelles of myeloid cells and converted prematurely to a supposedly biologically active form.
Inhibition of IL-6 signaling by a p38-dependent pathway occurs in the absence of new protein synthesis
Authors: Ahmed Simi T , Mayer Alexander , Ji Jong-Dae , Ivashkiv Lionel B 
Published: September 2022

AbstractNegative regulation of cytokine signaling is important for limiting the intensity and duration of cytokine action and for maintaining homeostasis. Several constitutive mechanisms for suppressing cytokine Jak-STAT signaling have been described. Inducible or regulated inhibition of cytokine signaling is equally important, and much attention has been focused on inhibition mediated through the induction of expression of suppressors of cytokine signaling (SOCS proteins). We have previously reported IL-1-induced inhibition of IL-6 signaling in monocytes, and herein we use inhibitors of protein synthesis to demonstrate that inhibition of IL-6 signaling can occur in the absence of new protein synthesis. Surprisingly, some protein synthesis inhibitors themselves inhibited IL-6 signaling rapidly, strengthening the conclusion that IL-6 signaling can be inhibited in the absence of protein synthesis. Inhibition of IL-6 signaling by IL-1 and protein synthesis inhibitors was dependent on the p38 stress kinase, and activation of p38 secondary to inducible expression of MKK6 was sufficient to inhibit IL-6 signaling. Inhibition was specific for IL-6, as induction of STAT activation by IFN-γ, IFN-α, and vanadate was not inhibited. IL-1-induced inhibition of IL-6 signaling was not mediated by the activation of tyrosine phosphatases or by p38-dependent activation of phospholipase A2 or cyclooxygenases, which could lead to indirect inhibition via production of prostaglandins. These results identify an inducible mechanism of inhibition of IL-6 signaling that is direct and independent of induction of negative regulators such as SOCS proteins. A role for p38 in mediating inhibition suggests that multiple cytokines and stress agents that activate p38 pathways in monocytes, such as IL-1, TNF, Toll-like receptors, and Fc receptors, can modulate Jak-STAT signaling by pleiotropic cytokines such as IL-6.
Mechanisms of TNF receptor-associated factor (TRAF) regulation in B lymphocytes
Authors: Bishop Gail A , Hostager Bruce S , Brown Kevin D 
Published: September 2022

AbstractA key component of signaling by members of the tumor necrosis factor receptor (TNF-R) family is interaction with the cytoplasmic adapter proteins known as TRAFs. Several proteins encoded by microbes also interact with TRAFs. A notable example is the CD40 receptor, expressed on antigen presenting cells and providing key activation signals in T cell-dependent B cell activation. CD40 signals to B cells are mimicked by a constitutively active viral protein produced by the Epstein-Barr virus. For each of these receptors, multiple mechanisms of TRAF regulation contribute to signal transduction and the ultimate effect on the B cell. Recent findings concerning these regulatory mechanisms are summarized in this overview.
IL-12 and IL-18 induce MAP kinase-dependent adhesion of T cells to extracellular matrix components
Authors: Ariel Amiram , Novick Daniela , Rubinstein Menachem , Dinarello Charles A , Lider Ofer , Hershkoviz Rami 
Published: September 2022

AbstractCytokines and chemokines play an essential role in recruiting leukocytes from the circulation to the peripheral sites of inflammation by modulating cellular interactions with endothelial cell ligands and extracellular matrix (ECM). Herein, we examined regulation of T cell adhesion to ECM ligands by two major proinflammatory cytokines, interleukin (IL)-12 and IL-18. IL-12 and IL-18 induced T cell adhesion to fibronectin (FN) and hyaluronic acid at low (pM) concentrations that were mediated by specific adhesion molecules expressed on the T cell surface, namely, β1 integrins and CD44, respectively. The induction of adhesion by IL-12 and IL-18 was inhibited by extracellular signal-regulated kinase and p38 mitogen-activated protein kinase inhibitors (PD098059 and SB203580, respectively). In contrast, IL-12- and IL-18-induced interferon-γ (INF-γ) secretion from T cells was inhibited by SB203580, but not by PD098059. It is interesting that low concentrations of IL-12 and IL-18 induced T cell adhesion to FN in a synergistic manner. Thus, in addition to the regulation of late inflammatory functions such as INF-γ production, IL-12 and IL-18, alone or in combination, regulate early inflammatory events such as T cell adhesion to inflamed sites.
Increased susceptibility to apoptosis and attenuated Bcl-2 expression in T lymphocytes and monocytes from patients with advanced chronic hepatitis C
Authors: Nakamoto Yasunari , Kaneko Shuichi , Kobayashi Kenichi 
Published: September 2022

AbstractSome viral infections are reported to influence the susceptibility of peripheral blood mononuclear cells (PBMC) to apoptosis, which is related to disease progression. The current study was designed to monitor apoptosis in separated PBMC subsets, CD4+ and CD8+ T lymphocytes, and CD14+ monocytes under apoptotic stimuli in patients with chronic hepatitis C. Apoptosis was induced by serum starvation and by incubation with anti-CD3 antibody and with phorbol 12-myristate 13-acetate. With the escalating severity of liver disease, susceptibility of all PBMC subsets to apoptosis increased under the apoptotic stimulus of serum starvation (P&lt;0.05). Consequently, increased susceptibility to apoptosis was associated with diminished intracellular expression of the antiapoptotic protein Bcl-2 (P&lt;0.05). The current observations demonstrate that the abnormality of PBMC subsets in undergoing apoptosis as a result of the down-regulation of Bcl-2 expression may contribute to viral persistence and progression of liver disease in chronic hepatitis C.
The role of P-selectin in experimental colitis as determined by antibody immunoblockade and genetically deficient mice
Authors: Gironella Meritxell , Mollà Meritxell , Salas Azucena , Soriano Antonio , Sans Miquel , Closa Daniel , Engel Pablo , Salas Antonio , Piqué Josep M , Panés Julián 
Published: September 2022

AbstractWe assessed the effects of genetic ablation of the P-selectin gene in comparison with functional immunoblockade of P-selectin on leukocyte recruitment and the course of disease in dextran sulfate sodium-induced colitis in mice. Compared with control antibody-treated wild-type (WT) mice, WT mice treated with anti-P-selectin antibody and P-selectin−/− mice had significantly decreased leukocyte rolling and adhesion in colonic venules and reduced clinical and pathological colitis scores. These reductions were more pronounced in anti-P-selectin-treated than in P-selectin−/− mice. In colonic endothelium, up-regulation of ICAM-1 was similar in WT and P-selectin−/− mice, but VCAM-1 up-regulation was significantly higher in the latter group. Lung leukocyte infiltration and VCAM-1 expression were increased only in P-selectin−/− colitic mice. Mortality was observed only in P-selectin−/− mice. Therefore, ablation of P-selectin function ameliorates colitis, but this protection is attenuated in P-selectin−/− mice, probably due to compensatory mechanisms that involve up-regulation of other adhesion molecules such as VCAM-1.
Neutrophil-Kupffer cell interaction: a critical component of host defenses to systemic bacterial infections
Authors: Gregory Stephen H , Wing Edward J 
Published: September 2022

AbstractMost bacteria that enter the bloodstream are taken up and eliminated within the liver. The specific mechanisms that underlie the role of the liver in the resolution of systemic bacterial infections remain to be determined. The vast majority of studies undertaken to date have focused on the function of resident tissue macrophages (Kupffer cells) that line the liver sinusoids. Indeed, it is often reported that Kupffer cells ingest and kill the bulk of organisms taken up by the liver. Recent studies indicate, however, that phagocytosis by Kupffer cells is not the principal mechanism by which organisms are eliminated. Rather, elimination depends on the complex interaction of Kupffer cells and bactericidal neutrophils that immigrate rapidly to the liver in response to infection. We discuss the critical role of neutrophil-Kupffer cell interaction in innate host defenses and, conceivably, the development and expression of adaptive immunity in the liver.
Binding of function-blocking mAbs to mouse and human P-selectin glycoprotein ligand-1 peptides with and without tyrosine sulfation
Authors: Thatte Aravinda , Ficarro Scott , Snapp Karen R , Wild Martin K , Vestweber Dietmar , Hunt Donald F , Ley Klaus F 
Published: September 2022

AbstractP-selectin glycoprotein ligand-1 (PSGL-1) mediates rolling of leukocytes on P-selectin-expressing endothelial cells under shear flow. Function-blocking monoclonal antibodies (mAbs) against mouse and human PSGL-1 recognize an anionic segment at the N-terminus of PSGL-1. High affinity interaction of PSGL-1 with P-selectin requires sulfation of tyrosines 46, 48, and 51 (human) or 54 and 56 (mouse). We tested binding of two anti-human (KPL1 and PL1) and two anti-mouse (4RA10 and 2PH1) PSGL-1 mAbs to synthetic peptides of N-terminus of human and mouse PSGL-1 and found binding to be independent of tyrosine sulfation. In peptide-blocking experiments, sulfated and nonsulfated human and mouse peptides competed with antibody binding to PSGL-1 expressed on myeloid cells. Arylsulfatase treatment significantly reduced P-selectin binding but had no effect on antibody binding. Our data show, in three independent assay systems, that function-blocking antibodies to mouse or human PSGL-1 do not require sulfation of N-terminal tyrosines for binding.
Molecular characterization and expression analysis of leucine-rich α2-glycoprotein, a novel marker of granulocytic differentiation
Authors: O'Donnell Lynn C , Druhan Lawrence J , Avalos Belinda R 
Published: September 2022

AbstractUsing data obtained from cDNA representational difference analysis to identify genes induced during neutrophilic differentiation of the 32D clone 3G (32Dcl3G) cells, we isolated cDNA clones for murine and human leucine-rich α2-glycoprotein (hLRG), a protein with unknown function purified 25 years ago. Expression of LRG during differentiation of 32Dcl3G cells preceded the expression of lactoferrin and gelatinase but followed myeloperoxidase. LRG transcripts were also detected in human neutrophils and progenitor cells but not in peripheral blood mononuclear cells. Notably, LRG expression was up-regulated during neutrophilic differentiation of human MPD and HL-60 cells but down-regulated during monocytic differentiation of HL-60 cells. The hLRG gene was localized to chromosome 19p13.3, a region to which the genes for several neutrophil granule enzymes also map. The putative promoter region of LRG was found to contain consensus-binding sites for PU.1, C/EBP, STAT, and MZF1. These results suggest that LRG is a novel marker for early neutrophilic granulocyte differentiation.
IL-10 expression profiling in human monocytes
Authors: Williams Lynn , Jarai Gabor , Smith Alexandra , Finan Peter 
Published: September 2022

AbstractInterleukin-10 (IL-10) is a potent anti-inflammatory cytokine with numerous immunomodulatory effects, including the inhibition of proinflammatory cytokine production. The mechanisms by which IL-10 exerts these effects still remain largely unknown. As there is evidence that suggests IL-10-mediated cytokine suppression requires the induction of an intermediate gene, we have used gene-chip technology to identify IL-10-inducible genes in human monocytes. We have been able to identify a total of 19 genes that are up-regulated in response to IL-10. Three of these genes had been identified previously: IL-1ra, suppressors of cytokine signaling-3, and CD163; however, the other 16 represent newly identified IL-10-responsive genes. Further analysis of the regulation of eight of these genes showed a remarkable specificity to regulation by lipopolysaccharides (LPS) and IL-10, but not by other anti-inflammatory mediators such as IL-4 and transforming growth factor-β, suggesting that two diverse stimuli such as IL-10 and LPS may engage common signaling mechanisms.
The chemoattractant Trp-Lys-Tyr-Met-Val-D-Met activates eosinophils through the formyl peptide receptor and one of its homologues, formyl peptide receptor-like 1
Authors: Svensson Lena , Dahlgren Claes , Wennerås Christine 
Published: September 2022

AbstractWhereas prokaryotes use L- and D-isomers of amino acids in their protein synthesis, eukaryotic proteins as a rule incorporate only L-isomers. Hence, D-isomers may constitute danger signals to the innate immune system. A D-methionine-containing peptide, Trp-Lys-Tyr-Met-Val-D-Met-NH2 (WKYMVm), has been shown to be a stronger activator of neutrophils than f-Met-Leu-Phe. The aim of this study was to compare the responsiveness of eosinophils to WKYMVm with that of neutrophils. The peptide was found to induce chemotaxis and respiratory burst in eosinophils. However, it did not mobilize granule constituents, as evidenced by a lack of eosinophil cationic protein, eosinophil peroxidase, and interleukin-5 in the supernatants of stimulated eosinophils. In contrast, WKYMVm caused the release of complement receptor 3 from secretory vesicles in neutrophils. Different members of the formyl peptide receptor family were preferentially engaged by the peptide in the two classes of granulocytes: the formyl peptide receptor itself in eosinophils and formyl peptide receptor-like 1 in neutrophils.
An essential role of macrophage inflammatory protein 1α/CCL3 on the expression of host's innate immunities against infectious complications
Authors: Takahashi Hitoshi , Tashiro Tsuguhiko , Miyazaki Masaru , Kobayashi Makiko , Pollard Richard B , Suzuki Fujio 
Published: September 2022

AbstractSepsis was induced by well-controlled cecal ligation and puncture (CLP) in macrophage inflammatory protein 1α (MIP-1α)/CCL3 knockout (CCL3−/−) and severe combined immunodeficiency (SCID) mice. CCL3−/− mice and their littermates (CCL3+/+ mice) treated with anti-CCL3 monoclonal antibodies were susceptible (0–20% survival) to CLP-induced sepsis, and CCL3−/− mice supplemented with recombinant (r)CCL3 (250 ng/mouse) and CCL3+/+ mice were resistant (70–80% survival). The resistance of SCID mice to CLP was markedly improved by the rCCL3 administration (88% survival), and SCID mice treated with saline were shown to be middling resistant to the same CLP (45% survival). However, the resistance of SCID-M mice (SCID mice depleted of the macrophage function) to CLP was not improved by the rCCL3 administration (11% survival), and 41% of SCID-M mice reconstituted with normal peritoneal macrophages and 79% of SCID-M mice inoculated with CCL3-treated peritoneal macrophages survived. In addition, the resistance of SCID-MN mice (SCID mice depleted of functional macrophages and neutrophils) to CLP was improved by the inoculation of CCL3-treated macrophages (78% survival), and all of SCID-MN mice inoculated with CCL3-treated neutrophils died. CCL3 is shown to be essential to the host resistance against bacterial sepsis. Macrophages but not neutrophils are highlighted as the major effector cells when protective innate immunities against sepsis are improved by CCL3.
Fraternal Forms and Forest Figures: Politics and Metapolitics in the Thought of Norman O. Brown
Authors: Carter Stephen 
Published: September 2022

AbstractThis essay explores Norman O. Brown's conception of politics and metapolitics. Brown describes politics via Freud's family romance, as a sphere of conflict between fathers and sons. The first part of the argument focuses on Brown's notion of the fraternal—collectivities organized via metaphorical extensions of brotherhood—as a central, underemphasized, and socially ambiguous aspect of his understanding of politics. The second part discusses Brown's use of figures drawn from ecological or environmental spaces, in particular trees and forests, to outline a notion of metapolitics, even while he also critiques conventional connections between the natural world and motherhood as still beholden to familial frameworks. The essay closes by arguing that Brown's forest imagery combines functional competent stewardship with playful wilderness pleasure, aiming to articulate forms of collective life that transcend Oedipal drama.
The Translatability of Experience
Authors: Mercier Lucie K. 
Published: September 2022

Abstract
Fanon considered that colonial alienation produced multiple forms of relational pathologies, many of which expressed themselves in and through blockages in communication rather than through explicit conflict. Exposing the role of language as a vector of racial violence and colonial oppression, Fanon also presented it as a potentially revolutionary medium of decolonization. The article has two aims: firstly, to give an account of Fanon's ongoing concern with language, in part by underscoring three very different influences in Fanon's expansive conception of its role—those of Aimé Césaire, Maurice Merleau-Ponty, and François Tosquelles. Secondly, the article aims to rearticulate the function of language in Fanon's theory of colonial disalienation by drawing on a specific trajectory in his clinico-political thought: from diagnoses of untranslatability or incommunicability to analyses of decolonization as the radical transformation of the subject's experience of language.
A dual involvement of Protocadherin 18a in stromal cell development guides the formation of a functional hematopoietic niche
Authors: Touret Anne-Lou , Vivier Catherine , Schmidt Anne , Herbomel Philippe , Murayama Emi 
Published: September 2022

ABSTRACT
Hematopoietic stem and progenitor cells emerge from the aorta and migrate to the caudal hematopoietic tissue (CHT) of zebrafish larvae, the hematopoietic equivalent of the mammalian fetal liver, for their proliferation and differentiation. We previously reported that somite-derived stromal cells were a key component of the CHT niche. Here, we found that the cell adhesion protein Protocadherin 18a (Pcdh18a) is expressed in the stromal cell progenitors (SCPs) emigrating from somites toward the future CHT. Deletion of most of the Pcdh18a intracellular domain caused a decrease in the number of SCPs, the directionality of their migration, and the cell-contact mediated repulsion that normally occurs between migrating SCPs. These defects were followed by abnormal morphogenesis of the venous plexus that forms the CHT framework, and the inability of the CHT to function as a niche for hematopoietic stem and progenitor cells. Finally, we found that the extracellular domain of Pcdh18a mediates trans heterophilic adhesion of stromal cells to endothelial cells in vivo and thereby the reticular versus perivascular fate of SCPs. Thus, Pcdh18a expression in SCPs is essential for the proper development of the hematopoietic niche.