bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological parameters of HIV-1 infection in primary intestinal lymphocytes and macrophages
Authors: Smith Phillip D , Meng Gang , Sellers Marty T , Rogers Tina S , Shaw George M 
Published: September 2022

Abstract
Mucosal surfaces are the portal of entry for most HIV-1 infections and play an important role in disease pathogenesis. To characterize the biological parameters of HIV-1 infection in mucosal cells, we used purified lamina propria lymphocytes and macrophages from normal human small intestine to determine the distribution of the HIV-1 receptor and coreceptors on intestinal mononuclear cells and the permissiveness of these cells to HIV-1 infection. Lamina propria lymphocytes expressed CD4, CCR5, and CXCR4. In contrast, lamina propria macrophages expressed CD4 but not CCR5 or CXCR4. Intestinal lymphocytes supported replication by R5 and X4 isolates of HIV-1, but lamina propria macrophages were permissive to neither. RANTES, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β inhibited infection of intestinal lymphocytes by BaL, indicating that R5 infection of the intestinal lymphocytes was mediated by CCR5. Thus, resident lamina propria lymphocytes, not macrophages, are the target mononuclear cell for HIV-1 infection in the intestinal mucosa during early HIV-1 infection.
HIV-1 Vpr regulates expression of β chemokines in human primary lymphocytes and macrophages
Authors: Muthumani Karuppiah , Kudchodkar Sagar , Papasavvas Emmanouil , Montaner Luis J , Weiner David B , Ayyavoo Velpandi 
Published: September 2022

Abstract
The HIV-1 vpr gene encodes a 14-kDa virion-packaged protein that has been implicated in viral pathogenesis. Vpr exhibits profound effects on human primary cells influencing proliferation, differentiation, apoptosis, and cytokine production, in part through NF-κB-mediated transcription. NF-κB, a potent transcription factor, activates many proinflammatory cytokines/chemokines upon infection. Here, we analyzed the effect of extracellular Vpr as well as the virion-associated Vpr on β chemokines (MIP-1α, MIP-1β, and RANTES) production in human macrophages and primary lymphocytes (PBLs). Macrophages and PBLs exposed to HIV-1 vpr+ viruses or to recombinant Vpr protein produced significantly less β chemokines compared with cells infected with HIV-1 vpr− viruses or irrelevant control protein (Gag)-exposed cells. These results suggest that a Vpr-mediated increase in virus replication could be in part through down-regulation of chemokine production.
Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia
Authors: Persidsky Yuri , Zheng Jialin , Miller Donald , Gendelman Howard E 
Published: September 2022

AbstractThe neuropathogenesis of HIV-1 infection revolves around the production of secretory factors from immune-activated brain mononuclear phagocytes (MP). MP-secreted chemokines may play several roles in HIV-1 encephalitis (HIVE). These can promote macrophage brain infiltration, blood-brain barrier (BBB) and neuronal dysfunction during HIV-1-associated dementia. We investigate how HIV-1-infected MP regulates the production of chemokines and how they influence HIV-1 neuropathogenesis. We demonstrate that HIV-1-infected and immune-activated MP (for example, microglia) and astrocytes produce β-chemokines in abundance, as shown in both laboratory assays and within infected brain tissue. HIV-1-infected microglia significantly modulate monocyte migration in a BBB model system and in brains of SCID mice with HIVE. HIV-1-infected MP down-regulate tight junction protein and special polarized transport systems on brain microvascular endothelial cells as shown in human autopsy brain tissue and in SCID mice with HIVE. Chemokines can damage neurons directly. Toxicity caused by binding of stromal-derived factor-1α to its receptor on neurons exemplifies such mechanism. In toto, these works underscore the diverse roles of chemokines in HIV-1 neuropathogenesis and lay the foundation for future therapeutic interventions.
Immunopharmacological activity ofEchinaceapreparations following simulated digestion on murine macrophages and human peripheral blood mononuclear cells
Authors: Rininger Joseph A , Kickner Shirley , Chigurupati Padmasree , McLean Anne , Franck Zsofia 
Published: September 2022

AbstractWe have investigated the immunostimulatory, anti-inflammatory, and antioxidant activities of variousEchinacea raw materials and commercially available products on murine macrophages and human peripheral blood mononuclear cells (PBMCs). To emulate oral dosing, a simulated digestion protocol was employed as a means of sample preparation.Echinacea-induced macrophage activation was used as a measure of immunostimulatory activity determined via quantitative assays for macrophage-derived factors including tumor necrosis factor α, interleukin (IL)-1α, IL-1β, IL-6, IL-10, and nitric oxide.Echinacea herb and root powders were found to stimulate murine macrophage cytokine secretion as well as to significantly enhance the viability and/or proliferation of human PBMCs in vitro. In contrast, Echinacea extracts chemically standardized to phenolic acid or echinocaside content and fresh pressed juice preparations were found to be inactive as immunostimulatory agents but did display, to varying degrees, anti-inflammatory and antioxidant properties.
Differential localization of protein kinase C isotypes in equine eosinophils and neutrophils
Authors: Greenaway E C , Cunningham F M , Goode N T 
Published: September 2022

AbstractPhorbol esters, which activate protein kinase C (PKC), stimulate equine eosinophil superoxide production and adherence. After showing that superoxide production could be inhibited by the nonselective PKC inhibitors, staurosporine and bisindolymaleimide I, the PKC isotypes in equine eosinophils were characterized, because evidence suggests that individual isotypes may play distinct roles in regulating eosinophil function. Western blots demonstrated that equine eosinophils expressed PKC α, β, δ, ɛ, ι, and ζ. However, unlike the equine neutrophil, the majority of the PKC was detected in the particulate fraction of the cell. Despite this unusual location, the PKC in equine eosinophils was activatable, suggesting that it is functionally competent. The regulatory role of PKC in equine eosinophils may reflect the association of activity with the particulate fraction and the profile of isotype expression.
IFN-α and IL-18 exert opposite regulatory effects on the IL-12 receptor expression and IL-12-induced IFN-γ production in mouse macrophages: novel pathways in the regulation of the inflammatory response of macrophages
Authors: Fantuzzi Laura , Puddu Patrizia , Varano Barbara , Del Cornò Manuela , Belardelli Filippo , Gessani Sandra 
Published: September 2022

AbstractWe characterized the IL-12 response of mouse macrophages in terms of modulation of IFN-γ production by cytokines (IFN-α and IL-18) and regulation of IL-12 receptor expression. β1 and β2 IL-12R chain mRNA expression increased with time in culture in the absence of exogenous stimulation, with concomitant acquisition of responsiveness to IL-12 for IFN-γ production. Expression of the IL-12R β1 chain mRNA was increased further following IL-12 treatment as a consequence of IFN-γ expression. IL-12 response was regulated differentially by IFN-α and IL-18. Neutralization of endogenous type I IFN increased IFN-γ secretion, whereas exogenous IFN-α reduced it. In contrast, IL-18 enhanced IFN-γ mRNA accumulation and IFN-γ secretion in IL-12-stimulated, but not -untreated, cultures. The opposite effects exerted by IFN-α and IL-18 mirror their mutual capacity of regulating—in a negative or positive manner, respectively—the expression of the IL-12R β1 chain. We suggest that differential regulation of IL-12 response by IFN-α and IL-18 can represent previously unrecognized regulatory mechanisms for maintaining suitable levels of differentiation/activation in macrophages.
Fibronectin-bound TNF-α stimulates monocyte matrix metalloproteinase-9 expression and regulates chemotaxis
Authors: Vaday Gayle G , Hershkoviz Rami , Rahat Michal A , Lahat Nitza , Cahalon Liora , Lider Ofer 
Published: September 2022

AbstractTumor necrosis factor α (TNF-α) is a proinflammatory cytokine implicated in the stimulation of matrix metalloproteinase (MMP) production by several cell types. Our previous studies demonstrated that TNF-α avidly binds fibronectin (FN) and laminin, major adhesive glycoproteins of extracellular matrix (ECM) and basement membranes. These findings suggested that TNF-α complexing to insoluble ECM components may serve to concentrate its activities to distinct inflamed sites. Herein, we explored the bioactivity and possible function of ECM-bound TNF-α by examining its effects on MMP-9 secretion by monocytes. Immunofluorescent staining indicated that LPS-activated monocytes deposited newly synthesized TNF-α into ECM-FN. FN-bound TNF-α (FN/TNF-α) significantly up-regulated MMP-9 expression and secretion by the human monocytic cell line MonoMac-6 and peripheral blood monocytes. Such secretion could be inhibited by antibodies that block TNF-α activity and binding to its receptors TNF RI (p55) and TNF RII (p75). Chemotaxis through ECM gels in the presence of soluble or bound TNF-α was inhibited by a hydroxamic acid inhibitor of MMPs (GM6001). It is interesting that, although the adhesion of MonoMac-6 cells to FN/TNF-α required functional activated β1 integrins, FN/TNF-α-induced MMP-9 secretion was independent of binding to β1 integrins, since MMP-9 secretion was unaffected by: (1) neutralizing mAb to α4, α5, and β1 subunits, which blocked cell adhesion; (2) a mAb that stimulated β1 integrin-mediated adhesion; and (3) binding TNF-α to the 30-kDa amino-terminal fragment of FN, which lacks the major cell adhesive binding sites. Thus, in addition to their cell-adhesive roles, ECM glycoproteins, such as FN, may play a pivotal role in presenting proinflammatory cytokines to leukocytes within the actual inflamed tissue, thereby affecting their capacities to secrete ECM-degrading enzymes. These TNF-α-ECM interactions may serve to limit the cytokine’s availability and bioactivity to target areas of inflammation.
Activating Ly-49D NK receptors: expression and function in relation to ontogeny and Ly-49 inhibitor receptors
Authors: Ortaldo John R , Winkler-Pickett Robin , Wiegand Gordon 
Published: September 2022

AbstractDevelopmental changes in the repertoire of activating Ly-49 family members have not been examined previously. In the present study, we have examined the expression and function of the activating Ly-49s (D and H) from birth through 8 weeks of age. We demonstrate that 1) activating Ly-49s are expressed early, 2) their expression intensity is not different from adult NK cells, and 3) activating receptors are functional. Examination of the inhibitory Ly-49s also demonstrated functional capacity immediately upon expression. To examine the kinetics of expression of the repertoire of activating Ly-49 members, we utilized five- and six-color flow cytometric analyses of NK cells from birth through adulthood. Previous studies examining the inhibitory Ly-49 repertoire have proposed that expression is regulated by the product rule. Our results indicated that Ly-49D, which recognizes H-2Dd, had a discordantly high coexpression of the inhibitory Ly-49s that recognized H-2Dd (Ly-49A and Ly-49G2). The product rule of Ly-49 expression does not explain the coexpression of selected activating and inhibitory receptors. This high level of coexpression of H-2Dd recognizing activating and inhibitory Ly- 49s suggests an in vivo selection or regulated coexpression.
Expression of mammalian defensin genes
Authors: Kaiser Vicki , Diamond Gill 
Published: September 2022

Abstract
Antimicrobial peptides are a prevalent mechanism of host defense found throughout nature. In mammals, defensins are among the most abundant of these broad-spectrum antibiotics, and are expressed in epithelial and hematopoietic cells. The defensin peptides are especially abundant in neutrophils; however, gene expression is limited to the promyelocyte stage. In epithelial cells, defensin genes are found as both constitutively expressed and inducible. Induction has been observedin vitro by stimulation with bacterial lipopolysaccharide as well as inflammatory mediators. In vivo, up-regulation of several defensin genes occurs in both infectious and inflammatory states. Gene regulation occurs via signal transduction pathways common to other innate immune responses, utilizing transcription factors such as nuclear factor (NF)-κB and NF interleukin-6. Together, the data suggest a broad-based innate host defense whereby potent antimicrobial peptides are present to prevent initial colonization by pathogenic microorganisms. In addition, the recognition of bacteria coupled with a nascent inflammatory response can bolster this defense by a coordinated up-regulation of the peptides.
Expression of α4β7 and E-selectin ligand by circulating memory B cells: implications for targeted trafficking to mucosal and systemic sites
Authors: Rott Lusijah S , Briskin Michael J , Butcher Eugene C 
Published: September 2022

AbstractWe have examined the expression of homing receptors on circulating memory B cells subsets. Blood IgD+ (naive) B cells homogeneously express a high level of intestinal homing receptor, α4β7, but IgD− (putative memory) B cells comprise distinct α4β7+ and α4β7− subsets. Naive and α4β7+ memory B cells but not α4β7− cells bind MAdCAM-1, suggesting that α4β7 expression may predict B cell intestinal homing. In contrast, α4β7+ and α4β7− B cells bind well to VCAM-1, possibly allowing recruitment of both subsets to extra-intestinal sites, including those tissues of the “common mucosal immune system” characterized by vascular VCAM-1 expression. sIgA+ B cells, which are associated with mucosal immunity in the gut and elsewhere, are heterogeneous in homing receptor expression—with discrete subsets expressing α4β7, L-selectin, and cutaneous lymphocyte antigen (CLA). sIgA+ CLA+ B cells are enriched by binding to E-selectin, suggesting that CLA may participate in B cell homing to nonintestinal mucosal tissues characterized by vascular E-selectin expression, such as chronically inflamed bronchial or oral mucosal. We conclude that circulating human peripheral blood memory B cells, like T cells, consist of discrete homing receptor-defined subsets. This diversity in homing phenotypes is apparent even among sIgA (presumptive mucosal) memory B cells, implying heterogeneity in trafficking mechanisms to different target mucosal surfaces.
Regulatory effects of fever-range whole-body hyperthermia on the LPS-induced acute inflammatory response
Authors: Ostberg Julie R , Taylor Shannon L , Baumann Heinz , Repasky Elizabeth A 
Published: September 2022

Abstract
The thermal component of fever is one of the most poorly understood aspects of inflammation. To evaluate the role of fever-range hyperthermia on acute inflammation, BALB/c and C57BL/6 mice were exposed to mild, long-duration whole-body hyperthermia (WBH), and serum concentrations of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), IL-1β, and the acute phase proteins (APPs) α1-acid glycoprotein and haptoglobin were analyzed. WBH alone did not affect serum concentrations of these cytokines or APPs when compared with controls. In contrast, when WBH was applied just after intraperitoneal administration of lipopolysaccharide (LPS), serum concentrations of TNF-α and IL-6 were greater than or equal to threefold higher in BALB/c mice compared with LPS-treated controls. LPS-induced IL-6 levels were also enhanced in WBH-treated C57BL/6 mice. However, APP levels were prolonged only in WBH-treated BALB/c mice. It is interesting thatin vitro hyperthermia treatment of LPS-stimulated peritoneal cells resulted in decreased cytokine production compared with controls. These results suggest that fever-range hyperthermia regulates acute inflammation in a mouse strain-specific manner that is more complex than that observed in vitro.
Neutrophil migration stimulates rat intestinal epithelial cell cytokine expression during helminth infection
Authors: Stadnyk Andrew W , Dollard Cheryl D , Issekutz Andrew C 
Published: September 2022

Abstract
We are interested in understanding the role of epithelial cells during inflammation, and we previously reported that rat small intestinal epithelial cells express interleukin-1β (IL-1β) during infection byTrichinella spiralis. We now report that the epithelium also produces the potent neutrophil chemotactic factor, macrophage inflammatory protein-2 (MIP-2), and an IL-1 antagonist: the type II IL-1 receptor. Consequently we investigated the pattern of neutrophil infiltration into the infected intestine, which closely paralleled the epithelial cytokine expression. Speculating that neutrophil infiltration may provoke epithelial cytokine expression, neutrophil migration into the infected gut was reduced by depleting circulating cells through the use of a specific antibody, or by preventing migration through the use of a function-blocking anti-CD18 monoclonal antibody. Either treatment reduced the number of neutrophils recoverable from the small intestinal epithelium and was paralleled by reduced mRNA levels for epithelial cytokines. These results demonstrate that neutrophil infiltration of the small intestinal epithelium contributes to the stimulation of epithelial cell cytokines.
Human lymphocytes stimulate prostacyclin synthesis in human umbilical vein endothelial cells. Involvement of endothelial cPLA2
Authors: Merhi-Soussi Faten , Dominguez Zury , Macovschi Olga , Dubois Madeleine , Savany Alain , Lagarde Michel , Prigent Annie-France 
Published: September 2022

Abstract
Prostacyclin (PGI2) contributes to the maintenance of a nonadhesive luminal surface in blood vessels due to its anti-platelet and vasodilatory properties. Here, we sought to determine whether peripheral blood lymphocytes (PBL) may regulate the PGI2 production of human umbilical vein endothelial cells (HUVEC). Cell-cell contact between HUVEC and lymphocytes markedly enhanced PGI2 synthesis as a function of the number of lymphocytes added. This stimulated synthesis was totally suppressed when lymphocytes and HUVEC were separated by a microporous insert. It was not due to prostaglandin H synthase up-regulation. The pretreatment of lymphocytes with the PGI2 synthase inhibitor tranylcypromine partially inhibited PGI2 synthesis (47%), suggesting a transcellular metabolism of the endothelial prostaglandin endoperoxide PGH2 by the lymphocyte PGI2 synthase. Experiments using [14C]arachidonate-labeled lymphocytes coincubated with unlabeled HUVEC, and [14C]arachidonate-labeled HUVEC coincubated with unlabeled lymphocytes showed that the arachidonic acid used for PGI2 synthesis was totally of endothelial origin. Furthermore, the PGI2 synthesis was strongly inhibited by the cytosolic phospholipase A2 inhibitor, MAFP and totally suppressed by the combination of the calcium chelators, BAPTA and EGTA. Collectively, these results suggest that lymphocytes trigger an outside-in signaling in endothelial cells involving cPLA2 activation. Overall, the switch-on for PGI2 synthesis induced by lymphocytes might serve as a protection against atherothrombogenesis.
Mechanisms mediating the effects of IL-3 gene expression on tumor growth
Authors: Wu Yuan-Zhau , Hong Ji-Hong , Huang Hsin-Hong , Dougherty Graeme J , McBride William H , Chiang Chi-Shiun 
Published: September 2022

AbstractIL-3 gene expression within tumors leads to host-cell infiltration, particularly by macrophages, slower tumor growth, and enhanced immunogenicity. Surprisingly, tumor-associated macrophages (TAMs) from within FSAN-JmIL3 tumors had decreased expression of TNF-α and iNOS. On short-term culture, TAMs from FSAN-JmIL3 tumors regained their capacity to produce TNF-α and NO, indicating that they were primedin vivo. In vitro experiments were unable to demonstrate differences between FSAN-JmIL3 and FSAN tumor cells in their ability to stimulate TNF-α production by TAMs. In the absence of evidence that TAM activation was responsible for the slower growth of FSAN-JmIL3 tumors, the response of tumor cells to these effector molecules was studied. TNF-α and NO were cytotoxic for FSAN-JmIL3 cells but growth stimulatory for FSAN. These tumor-related phenotypic changes may contribute as much if not more than functional changes in host infiltrating cells to the slower growth of FSAN-JmIL3 tumorsin vivo.
Differential chemokine response of human monocytes to yeast and hyphal forms ofCandida albicansand its relation to the β-1,6 glucan of the fungal cell wall
Authors: Torosantucci Antonella , Chiani Paola , Cassone Antonio 
Published: September 2022

AbstractHyphae formation from yeast cells is a virulence trait enabling the human opportunistic pathogen Candida albicans to invade host tissues. Hyphal cells proved to be much less efficient than yeast cells in stimulating production of macrophage inflammatory protein-1α (MIP-1α), MIP-1β, interleukin-8 (IL-8), and particularly, monocyte chemotactic protein-1 (MCP-1) by human monocyte. This different stimulation did not depend on the monocyte inability to ingest the hyphae nor did it imply hyphal resistance to the extracellular killing by the monocytes. Purified hyphal and yeast cell walls reproduced the differences shown by the intact cells, and chemical-enzymatic dissection of cell wall components suggested that cell wall β-1,6 rather than β-1,3 glucan was the main chemokine inducer. Coherently, immunofluorescence studies with an anti β-1,6 glucan serum showed that the surface expression of this polysaccharide was much lower on hyphae than on yeast cells. By minimizing chemokine induction, the formation of hyphal filaments might facilitate C. albicans escaping from host immunity.
Pivotal role of 5-lipoxygenase in the activation of human eosinophils: platelet-activating factor and interleukin-5 induce CD69 on eosinophils through the 5-lipoxygenase pathway
Authors: Urasaki Tetsuya , Takasaki Jun , Nagasawa Toshiro , Ninomiya Haruhiko 
Published: September 2022

AbstractCD69 is an activation-related cell surface molecule on human eosinophils. It has been reported that interleukin (IL)-5, but not platelet-activating factor (PAF), can induce CD69 on human eosinophils in vitro. In this study, PAF induced CD69 intensely on eosinophils from patients with hypereosinophilic syndrome (HES), while only weakly on those from normal donors. Because HES eosinophils contain abundant cytosolic phospholipase A2 (cPLA2) and 5-lipoxygenase (5-LO), we examined the roles of several enzymes involved in the metabolism of arachidonic acid in the PAF- or IL-5-induced CD69 expression on eosinophils. The CD69 expression induced by PAF and IL-5 on HES eosinophils and that by IL-5 on normal eosinophils were both inhibited by AA861 and MK-886, inhibitors of 5-LO activity. In addition, AACOCF3, a selective cPLA2 inhibitor, inhibited IL-5-induced CD69 expression on normal eosinophils, although it hardly affected either IL-5- or PAF-induced CD69 expression on HES eosinophils. Moreover, PAF alone induced CD69 only weakly on normal eosinophils, but exogenous arachidonic acid remarkably enhanced PAF-induced CD69 expression on them. These findings suggest that IL-5 activates both cPLA2 and 5-LO but PAF activates only 5-LO. It is suggested that 5-LO plays a critical role in the induction of CD69 on eosinophils.