bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukocyte antimicrobial peptides: multifunctional effector molecules of innate immunity
Authors: Risso Angela 
Published: September 2022

AbstractAntimicrobial peptides are effector molecules of innate immunity that provide a first line of defense against pathogens. In mammals, they are stored in granules of leukocytes and are present in those sites that are exposed to microbial invasion, such as mucosal surfaces and skin. In the last decade, biochemical investigations and recombinant DNA technology have allowed the identification and characterization of several antimicrobial peptides from various animal and vegetal species. Most of the mammalian peptides have been grouped in two broad families: defensins and cathelicidin-derived peptides. Functional studies have shown that the toxicity mechanisms for many peptides consist of a rapid permeabilization of the target cell membrane. In addition to their microbicidal activity, some members of both families are multifunctional molecules, playing a modulating role in the inflammation and the antigen-driven immune response.
Characterization of thyroid fibrosis in a murine model of granulomatous experimental autoimmune thyroiditis
Authors: Chen Kemin , Wei Yongzhong , Sharp Gordon C , Braley-Mullen Helen 
Published: September 2022

AbstractThis study was initiated to identify and characterize thyroid fibrosis in a murine model of granulomatous experimental autoimmune thyroiditis (G-EAT) and determine if TGF-β1 might be involved in fibrosis. G-EAT was induced by transfer of mouse thyroglobulin-sensitized spleen cells activated in vitro with thyroglobulin, anti-IL-2R, and IL-12. There was almost complete destruction of thyroid follicles, leading to fibrosis of the gland and reduced serum T4 levels. Fibrosis was confirmed by staining for collagen and α smooth-muscle actin, a marker of myofibroblasts. Kinetic studies characterized the onset and development of thyroid fibrosis. TGF-β1 was increased at mRNA and protein levels, and expression of TGF-β1 protein paralleled G-EAT severity. Comparison of staining patterns showed that TGF-β1 was expressed in areas of myofibroblast and collagen accumulation, implying that TGF-β1 may play a role in fibrosis in G-EAT. Further studies demonstrated that myofibroblasts, macrophages, and thyrocytes contributed to TGF-β1 production. This provides an excellent model to study the mechanisms of fibrosis associated with autoimmune damage.
TAK1 regulates multiple protein kinase cascades activated by bacterial lipopolysaccharide
Authors: Lee Jongdae , Mira-Arbibe Laurence , Ulevitch Richard J 
Published: September 2022

AbstractDuring inflammation the balance between cell activation and cell death is determined by the tight regulation of multiple intracellular enzyme cascades. Key regulatory steps often involve protein kinases. We show that the prototypical pro-inflammatory molecule, bacterial lipopolysaccharide, activates multiple protein kinases such as p38, JNK, IKK-β, and PKB/Akt via transforming growth factor β-activated kinase-1 (TAK1). We also show that TAK1 plays an important role in similar activation pathways triggered by interleukin-1. Thus TAK1 must be considered as an important component of intracellular signaling pathways in cells involved in host responses to physiological and/or environmental stress signals during inflammation.
Activated human platelets express Fas-L and induce apoptosis in Fas-positive tumor cells
Authors: Ahmad Rasheed , Menezes José , Knafo Laurent , Ahmad Ali 
Published: September 2022

AbstractIn addition to their role in hemostasis and thrombosis, platelets are important modulators of immune and inflammatory responses. We provide evidence here that human platelets contain abundant quantities of Fas-L, and upon activation, they express it on their surface as well as release it into medium. This surface-expressed Fas-L is biologically active and can induce apoptosis in Fas-positive human tumor cells. Therefore, activated platelets may represent an important player in Fas/Fas-L-mediated apoptosis.
Tumor cell-derived TGF-β and IL-10 dysregulate paclitaxel-induced macrophage activation
Authors: Mullins David W , Martins Ryan S , Burger Carol J , Elgert Klaus D 
Published: September 2022

AbstractPaclitaxel (TAXOL™) activates in vitro macrophage (Mø) expression of proinflammatory and cytotoxic mediators, including IL-12, tumor necrosis factor α (TNF-α), and nitric oxide (NO). However, tumors dysregulate Mø through soluble suppressor molecules, and it is possible that tumors evade paclitaxel-mediated immune effector function through the production of immunomodulatory molecules and inhibition of Mø function in situ. Because Mø activation in the tumor microenvironment is a desirable goal of anti-tumor immunotherapy, we evaluated whether tumor-derived immunomodulatory factors dysregulate paclitaxel-mediated Mø activation. Tumor cell-derived supernatant suppressed paclitaxel's capacity to induce IL-12, TNF-α, and NO production by RAW264.7 Mø. Tumor factors also dysregulated paclitaxel-induced expression of a HIV-LTR, promoter-driven luciferase construct in RAW264.7 Mø, suggesting that tumors may inhibit a broad range of Mø functionality. Depletion studies revealed that IL-10 and transforming growth factor-β1 (TGF-β1), but not prostaglandin E2 (PGE2), impaired paclitaxel-mediated activation, suggesting that abrogation of these factors in situ might restore paclitaxel's activating capacity and enhance anti-tumor efficacy.
Impaired IL-15 production associated with susceptibility of murine AIDS to mycobacterial infection
Authors: Umemura Masayuki , Hirose Kenji , Wajjwalku Worawidh , Nishimura Hitoshi , Matsuguchi Tetsuya , Gotoh Yoshitaka , Takahashi Masahide , Makino Masahiko , Yoshikai Yasunobu 
Published: September 2022

AbstractLP-BM5 murine leukemia virus (MuLV) injection causes murine AIDS (MAIDS), a disease characterized by many functional abnormalities of immunocompetent cells. We show that MAIDS mice are susceptible to Mycobacterium bovis Bacille Calmette-Guérin (BCG) infection as assessed by survival rate and bacterial counts. The peritoneal exudate macrophages from MAIDS mice produced a significant level of interleukin (IL)-12 soon after inoculation with BCG, whereas IL-15 and tumor necrosis factor (TNF) production were severely impaired in BCG-infected MAIDS mice. The appearance of natural killer (NK) and CD4+ T helper type 1 (Th1) cells specific for mycobacterial antigen were depressed in MAIDS mice after BCG infection. Thus, it appeared that impaired production of IL-15, besides other inflammatory cytokines, in MAIDS mice may be involved in the poor responses of the NK and Th1 cells, resulting in an increased susceptibility to BCG.
Autocrine action of IL-10 suppresses proinflammatory mediators and inflammation in the HSV-1-infected cornea
Authors: Yan Xiao-Tian , Zhuang Minsheng , Oakes John E , Lausch Robert N 
Published: September 2022

AbstractWe investigated whether IL-10 produced endogenously would influence the development of HSV-1-induced acute corneal disease. Murine corneal epithelial cells and fibroblasts cultured in vitro expressed IL-10 mRNA and protein constitutively and also IL-10 receptors. Inclusion of IL-10 neutralizing antibody in the culture medium significantly (p&lt;0.05) enhanced TNF-α-induced IL-6 and MIP-2 production by both corneal cell types. Endogenous IL-10 synthesis, which also occurred in vivo, was not modulated by Herpes virus infection or by depletion of neutrophils or natural killer cells. Antibody to IL-10 given locally at the time of HSV-1 intracorneal infection was associated with significantly (p&lt;0.05) enhanced production of IL-6, MIP-2, and MIP-1α, increased neutrophil infiltration, and more extensive corneal disease. Similarly, mice with a disrupted IL-10 gene developed more severe corneal disease than wild-type controls. Collectively, these observations suggest that locally produced IL-10 can act in an autocrine/paracrine fashion to down-regulate the production of proinflammatory mediators and thus limit corneal inflammation.
Differences in the induction of CD8+ T cell responses by subpopulations of dendritic cells from afferent lymph are related to IL-1α secretion
Authors: Hope Jayne C , Sopp Paul , Collins Robert A , Howard Chris J 
Published: September 2022

AbstractThe major subset of dendritic cells (DC) from bovine afferent lymph expresses the SIRPα MyD-1 antigen, but not CD11a or the antigen recognized by mAb CC81, and potently stimulates CD4+ and CD8+ T lymphocyte proliferation. The minor subpopulation, that is CD11a+CC81+MyD-1−, effectively stimulates CD4+ but not CD8+ T lymphocyte proliferation. CD11a+CC81+MyD-1− DC did not induce anergy or death or secrete an inhibitory factor. However, supernatant from cultures of CD8+ T cells with CD11a−CC81−MyD-1+ DC significantly enhanced proliferation of CD8+ T cells in response to CD11a+CC81+MyD-1− DC, an effect that was blocked by interleukin (IL)-1α, but not IL-1β, specific mAb. The proliferation of CD8+ T cells with CD11a+CC81+MyD-1− DC was also enhanced by adding IL-1α. IL-1β slightly enhanced proliferation, whereas IL-2, IL-6, IL-12, and IL-15 had no effect. We conclude that the failure to stimulate CD8+ T cell proliferation results from the lack of IL-1α synthesis by this population, which may have important consequences in vivo.
Phagocytosis and killing ofMycobacterium aviumcomplex by human neutrophils
Authors: Hartmann Pia , Becker Ralph , Franzen Caspar , Schell-Frederick Elisabeth , Römer Jens , Jacobs Michaela , Fätkenheuer Gerd , Plum Georg 
Published: September 2022

AbstractOrganisms belonging to the Mycobacterium avium complex (MAC) cause life-threatening bacteremia in immunocompromised patients. Monocytes and macrophages are thought to be responsible for ingestion and killing of MAC. However, it has been suggested that neutrophils may play a role in the early immune response to MAC infection. Here, neutrophils in autologous plasma were incubated (at 0 and 37°C) withM. avium labeled with Auramine O, a potent fluorochrome. Neutrophil phagocytosis was measured by flow cytometry. Neutrophils incubated at 37°C showed an increase in fluorescence over time with a maximum at 15 min, whereas neutrophils on ice showed no time-dependent increase in FL1. At 15 min Fl 1 at 37°C was twice as high as FL1 at 0°C. Examination under the fluorescent microscope showed multiple intracellular fluorescent mycobacteria. Results in nine independent experiments showed time-dependent decrease of colony-forming units in neutrophil-associated live M. avium. Significant killing was observed within 30 min and was complete by 120 min. Observation by electron microscopy clearly confirmed the presence of intraphagosomal MAC, both intact and with evidence of degradation. These data demonstrate that MAC is rapidly phagocytized and killed by human neutrophils. The newly established flow cytometry method should be useful in further studies of neutrophil function and of the role of G-CSF and other cytokines in MAC disease.
CD86 expression correlates with amounts of HIV produced by macrophagesin vitro
Authors: Wang Xiaoping , Lewis Dorothy E 
Published: September 2022

AbstractPrimary macrophages from different donors produce variable levels of HIV; however, the mechanisms are unclear. We tested whether variations in cell-surface or cell-cycle characteristics influenced HIV production. We found that greater basal proliferation of the macrophages prior to infection resulted in more arrested in G2M 3 days post-infection (r2=0.7,P&lt;0.04). Likewise, the number of G2M-arrested macrophages correlated with p24 production (r2=0.78,P&lt;0.02) and apoptosis (r2=0.67,P&lt;0.05) later in the infection. Serum-starvation or reduction, which limit HIV spread, reduced G2M arrest and HIV amounts. Surprisingly, the amount of HIV produced correlated with expression levels of the costimulating ligand, CD86, but not with other important molecules, including class II, CD40, or CD54 (r2=0.96, P&lt;0.0005). These data establish donor characteristics related to variable HIV production in vitro and suggest that altered expression of costimulatory ligands may influence HIV production in vivo.
Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action?
Authors: Caldefie-Chezet F , Poulin A , Tridon A , Sion B , Vasson M-P 
Published: September 2022

AbstractIt is well known that leptin, the ob gene product, is involved in the regulation of food intake and thermogenesis. Recent studies also demonstrate that leptin may be able to modulate functions of cells involved in nonspecific immune response such as phagocytosis and secretion of cytokines by macrophages. This and the prominent implication of polymorphonuclear neutrophils (PMNs) in infectious response suggested a possible role of leptin as a modulator of PMN functions. We detected a leptin receptor on the PMN membrane by immunocytochemistry with an anti-leptin receptor. Using chemiluminescence we then demonstrated that leptin enhances oxidative species production by stimulated PMNs. These results show for the first time that a functional leptin receptor is present on PMNs and that leptin may be able to influence their oxidative capacity.
Leukocyte-specific gene 1 protein (LSP1) is involved in chemokine KC-activated cytoskeletal reorganization in murine neutrophilsin vitro
Authors: Hannigan Michael , Zhan Lijun , Ai Youxi , Huang Chi-Kuang 
Published: September 2022

AbstractLeukocyte-specific gene 1 protein (LSP1) is a cytoskeletal-associated protein of leukocytes that in vitro cross-links F-actin into extensively branched bundles of mixed polarity. In this study, we examined chemotaxis and superoxide production in neutrophils prepared from wild-type (WT) and Lsp1 knockout mice. Compared to WT neutrophils, Lsp1-/- neutrophils showed impairment in both migration speed and chemotaxis direction during chemokine KC-directed chemotaxis. When examined by confocal microscopy, chemotaxing Lsp1-/- neutrophils showed abnormal morphologies. They had discontinuous primary actin-rich cortexes and large membrane protrusions. When stimulated by phorbol 12-myristate 13-acetate (PMA), Lsp1-/- peritoneal neutrophils produce more superoxide than WT. The data presented suggest that LSP1 plays important roles in the regulation of neutrophil morphology, motility, and superoxide production.
Induction of soluble antitumoral mediators by synthetic analogues of bacterial lipoprotein in bone marrow-derived macrophages from LPS-responder and -nonresponder mice
Authors: Pfannes Silke D C , Müller Bernd , Körner Stephan , Bessler Wolfgang G , Hoffmann Petra 
Published: September 2022

AbstractMacrophage-dependent antitumoral activity is partly mediated by soluble factors including cytokines, reactive-oxygen intermediates (ROIs), and reactive-nitrogen intermediates (RNIs). Activation of macrophages for tumor cytotoxicity can be achieved with various bacterial compounds, such as lipopolysaccharides (LPSs), muramyl-dipeptides, and lipopeptides. We studied the production and release of oxygen radicals, nitric oxide, and tumor necrosis factor α (TNF-α) by bone marrow-derived macrophages (BMDMs) of different mouse inbred strains after they were stimulated with the lipopeptide P3CSK4, a water-soluble synthetic analogue of the lipidated N terminus of bacterial lipoprotein. The lipopeptide was able to induce a strong, long lasting release of oxygen radicals in BALB/c mouse macrophages. Furthermore, it induced nitric oxide release from BMDMs of several mouse strains (BALB/c, C57Bl/6, C57Bl/10ScSn, Sv129, NMRI, and LPS-nonresponder C57Bl/10ScCr). Stimulation with P3CSK4 also resulted in comparable production of TNF-α in LPS-responder and nonresponder BMDMs from C57Bl/10ScSn mice and C57Bl/10ScCr mice, respectively. All three antitumoral mediators reached functional levels or concentrations as shown by the strong cytostatic/cytotoxic activity of lipopeptide-activated macrophages for the cell lines Abelson 8-1, M12.5/P815, and L929, which are sensitive to ROIs, nitric oxide, and TNF-α, respectively. We found that synthetic lipopeptides can induce the secretion of effective levels of soluble tumor-cytotoxic/cytostatic mediators in BMDMs of LPS-responsive and, of particular interest, also of LPS-unresponsive mice. This result could indicate that the highly effective bacterial-macrophage activators P3CSK4 and LPS use different receptors and/or different intracellular signal transduction pathways.
Inflammatory macrophage nuclear factor-κB and proteasome activity are inhibited following exposure to inhaled isobutyl nitrite
Authors: Ponnappan Usha , Soderberg Lee S F 
Published: September 2022

AbstractA history of abuse of nitrite inhalants has been correlated with HIVseropositivity and Kaposi's sarcoma. A series of 14 daily, 45-minexposures of mice to 900-ppm isobutyl nitrite in an inhalation chamberreduced the number of peritoneal exudate macrophages (PEM) by 35% andthe number of resident peritoneal macrophages (RPM) by 18%. Althoughthe tumoricidal activity of RPM was not affected by the inhalant, thecytotoxicity of PEM was reduced by 26%. The induction of nitric oxide(NO) and the inducible NO synthase (iNOS) protein in PEM were inhibitedby the inhalant to a similar extent. Inhibition of NF-κB activationin PEM from mice exposed to the inhalant corresponded to reduceddegradation of the NF-κB inhibitor, IκBα. Proteasome-associated,enzymatic activity was compromised in PEM from inhalant-exposed mice,suggesting that inhaled isobutyl nitrite compromised macrophage,tumoricidal activity by inhibiting proteasomal degradation of theNF-κB inhibitor, IκBα.
Green tea polyphenol (−)-epigallocatechin-3-gallate treatment to mouse skin prevents UVB-induced infiltration of leukocytes, depletion of antigen-presenting cells, and oxidative stress
Authors: Katiyar Santosh K , Mukhtar Hasan 
Published: September 2022

AbstractUltraviolet (UV) radiation-induced infiltrating leukocytes, depletionof antigen-presenting cells, and oxidative stress in the skin play animportant role in the induction of immune suppression andphotocarcinogenesis. Earlier we have shown that topical application ofpolyphenols from green tea or its major chemopreventive constituent(−)-epigallocatechin-3-gallate (EGCG) prevents UV-B-inducedimmunosuppression in mice. To define the mechanism of prevention, wefound that topical application of EGCG (3 mg/mouse/3 cm2 ofskin area) to C3H/HeN mice before a single dose of UV-B (90mJ/cm2) exposure inhibited UV-B-induced infiltration ofleukocytes, specifically the CD11b+ cell type, and myeloperoxidaseactivity, a marker of tissue infiltration of leukocytes. EGCG treatmentwas also found to prevent UV-B-induced depletion in the number ofantigen-presenting cells when immunohistochemically detected as classII MHC+ Ia+ cells. UV-B-induced infiltrating cell production of H2O2 and nitric oxide (NO) was determined as amarker of oxidative stress. We found that pretreatment of EGCGdecreased the number of UV-B-induced increases inH2O2-producing cells and inducible nitric oxidesynthase-expressing cells and the production of H2O2 and NO in both epidermis and dermis at aUV-B-irradiated site. Together, these data suggest that prevention of UV-B-induced infiltrating leukocytes, antigen-presenting cells, andoxidative stress by EGCG treatment of mouse skin may be associated withthe prevention of UV-B-induced immunosuppression andphotocarcinogenesis.
Effect of vibrational stress and spaceflight on regulation of heat shock proteins hsp70 and hsp27 in human lymphocytes (Jurkat)
Authors: Cubano Luis A , Lewis Marian L 
Published: September 2022

AbstractHeat shock protein levels are increased in cells as a result of exposure to stress. To determine whether heat shock protein regulation could be used to evaluate stress in cells during spaceflight, the response of Jurkat cells to spaceflight and simulated space shuttle launch vibration was investigated by evaluating hsp70 and hsp27 gene expression. Gene expression was assessed by reverse transcription-polymerase chain reaction using mRNA extracted from vibrated, nonvibrated, space-flown, and ground control cells. Results indicate that mechanical stresses of vibration and low gravity do not up-regulate the mRNA for hsp70, although the gene encoding hsp27 is up-regulated by spaceflight but not by vibration. In ground controls, the mRNA for hsp70 and hsp27 increased with time in culture. We conclude that hsp70 gene expression is a useful indicator of stress related to culture density but is not an indicator of the stresses of launch vibration or microgravity. Up-regulation of hsp27 gene expression in microgravity is a new finding.
Interleukin-18 expression induced by Epstein-Barr virus-infected cells
Authors: Yao Lei , Setsuda Joyce , Sgadari Cecilia , Cherney Barry , Tosato Giovanna 
Published: September 2022

AbstractHuman Epstein-Barr virus (EBV)-negative Burkitt lymphomas cells usually grow as malignant subcutaneous tumors in athymic mice, but these tumors regress when the Burkitt cells are injected in conjunction with EBV-positive lymphoblastoid cells or when the Burkitt cells are transfected with the EBV latent membrane protein-1 (LMP-1) gene. Tumor regression is mediated, in part, by murine interferon γ (IFN-γ) and the IFN-γ-induced murine chemokine IFN-γ-inducible protein-10 (IP-10). The mechanisms by which EBV-LMP-1 promotes the expression of IFN-γ has remained unclear. Here we show that murine interleukin (IL)-18 was consistently expressed in regressing Burkitt tumors but was either expressed at low levels or absent from progressively growing Burkitt tumors. By immunohistochemical methods, IL-18 protein was visualized in regressing but not in progressively growing Burkitt tumors. In contrast, IL-12 p35 and IL-12 p40 were only rarely expressed in regressing Burkitt tumors. In splenocyte cultures, EBV-infected lymphoblastoid cells and LMP-1-transfected Burkitt cells promoted the expression of IL-18 but not the expression of IL-12 p35 and IL-12 p40. A neutralizing antibody directed at murine IL-18 reduced murine IP-10 expression induced by EBV-immortalized cells in splenocyte cultures. These results provide evidence for IL-18 expression in response to a viral latency protein and suggest that IL-18 may play an important role as an endogenous inducer of IFN-γ expression, thereby contributing to tumor regression.
Novel chemokine functions in lymphocyte migration through vascular endothelium under shear flow
Authors: Cinamon Guy , Grabovsky Valentin , Winter Eitan , Franitza Suzanna , Feigelson Sara , Shamri Revital , Dwir Oren , Alon Ronen 
Published: September 2022

AbstractThe recruitment of circulating leukocytes at vascular sites in target tissue has been linked to activation of Gi-protein signaling in leukocytes by endothelial chemokines. The mechanisms by which apical and subendothelial chemokines regulate leukocyte adhesion to and migration across endothelial barriers have been elusive. We recently found that endothelial chemokines not only stimulate integrin-mediated arrest on vascular endothelial ligands but also trigger earlier very late antigen (VLA)-4 integrin-mediated capture (tethering) of lymphocytes to vascular cell adhesion molecule 1 (VCAM-1)-bearing surfaces by extremely rapid modulation of integrin clustering at adhesive contact zones. This rapid modulation of integrin avidity requires chemokine immobilization in juxtaposition with the VLA-4 ligand VCAM-1. We also observed that endothelial-bound chemokines promote massive lymphocyte transendothelial migration (TEM). It is interesting that chemokine-promoted lymphocyte TEM requires continuous exposure of lymphocytes but not of the endothelial barrier to fluid shear. It is noteworthy that lymphocyte stimulation by soluble chemokines did not promote lymphocyte TEM. Our results suggest new roles for apical endothelial chemokines both in triggering lymphocyte capture to the endothelial surface and in driving post-arrest events that promote lymphocyte transmigration across endothelial barriers under shear flow.