bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo GM-CSF prevents dexamethasone suppression of killing ofAspergillus fumigatusconidia by bronchoalveolar macrophages
Authors: Brummer Elmer , Maqbool Anjum , Stevens David A 
Published: September 2022

AbstractDexamethasone (DEX) is a potent immunosuppressive agent used in the treatment of several disorders. However, despite its beneficial effects, DEX puts patients at risk for opportunistic infections, especially pulmonary aspergillosis. Previously we reported that in vitro granulocyte-macrophage colony-stimulating factor (GM-CSF) blocks the immunosuppressive action of DEX on bronchoalveolar macrophages (BAMs). Here we report that BAMs freshly isolated from mice treated intraperitoneally with DEX for 24 h had significantly (P&lt;0.01) reduced killing of conidia, i.e., 15 ± 5% conidia killed by BAMs from DEX-treated mice versus 35 ± 3% by BAMs from mice given saline, 38 ± 5% by BAMs from mice given GM-CSF, and 39 ± 1% by BAMs from mice given both DEX and GM-CSF. On the other hand, in another compartment GM-CSF could not block the DEX reduction of spleen weight and spleen cellularity. Unlike GM-CSF, granulocyte colony-stimulating factor did not block DEX suppression of BAMs. GM-CSF given 24 h before DEX resulted in blocking of DEX suppression of BAM conidiacidal activity. However, when DEX was given 24 h before GM-CSF, DEX suppression of BAM was not reversed. These data show that GM-CSF in vivo blocks the in vivo immunosuppressive effects of DEX on BAM killing of conidia and suggest a potential use of GM-CSF in patients at risk for aspergillosis due to immunosuppressive DEX treatment.
The contribution of oxidative stress in apoptosis of human-cultured astroglial cells induced by supernatants of HIV-1-infected macrophages
Authors: Mollace Vincenzo , Salvemini Daniela , Riley Dennis P , Muscoli Carolina , Iannone Michelangelo , Granato Teresa , Masuelli Laura , Modesti Andrea , Rotiroti Domenicantonio , Nisticó Robert , Bertoli Ada , Perno Carlo-Federico , Aquaro Stefano 
Published: September 2022

AbstractApoptosis of neurons and astrocytes has been found in patientsundergoing AIDS dementia complex. We demonstrated that supernatantsfrom human primary macrophages (M/M) infected by HIV-1 lead humanastroglial cells to oxidative stress, as shown by elevated levels of malondialdehyde, and then to apoptosis. Electron microscopy ofastrocytes shortly incubated with HIV-1-infected M/M supernatantsshowed apoptotic blebbing, cytoplasmic loss, and chromatincondensation. Apoptosis was antagonized by pretreating astrocytes withthe nonpeptidic superoxide dismutase (SOD) mimetic M40401 but notwith anti-HIV-1 compounds, thus showing that apoptosis of astrocytesdriven by HIV-1-infected M/M supernatants is mainly mediated byabnormal production of superoxide anions without relationship to HIV-1replication in such cells. Overall results support the role ofoxidative stress mediated by HIV-1-infected M/M as one of the leadingcauses of neurodegeneration in patients with HIV-1 and suggest the useof nonpeptidic SOD mimetics to counteract HIV-1-related neurologicaldisorders.
The loss of IAP expression during HL-60 cell differentiation is caspase-independent
Authors: Doyle B T , O'Neill A J , Newsholme P , Fitzpatrick J M , Watson R W G 
Published: September 2022

AbstractHuman promyelocytic leukaemia cells (HL-60) differentiate into neutrophil-like cells that die spontaneously by apoptosis when treated with retinoic acid (RA). Inhibitors of apoptosis proteins (IAP) bind to and inhibit caspases 3, 7, and 9 activity and the induction of apoptosis. In this study, we demonstrate that undifferentiated HL-60 cells express IAP. During their differentiation, IAP expression is decreased at the mRNA and protein levels. In addition, we show that there is a corresponding increase in the expression and functional activity of active caspases 3 and 9. This activity was associated with the cleavage of XIAP, NAIP, and cIAP-2. Most importantly, we demonstrate that blocking caspase activity does not alter the decrease in IAP protein expression during differentiation but prevents caspase activation, IAP cleavage, and the induction of apoptosis. This result shows that the loss of IAP expression is independent of the induction of apoptosis and is solely related to the differentiation process. However, IAP cleavage is caspase-dependent. Terminal differentiation results in an altered apoptotic phenotype that is associated with the induction of HL-60 cell apoptosis.
The synthetic chemoattractant peptide, Trp-Lys-Tyr-Met-Val-d-Met, enhances monocyte survival via PKC-dependent Akt activation
Authors: Bae Yoe-Sik , Kim Youndong , Park Jun Chul , Suh Pann-Ghill , Ryu Sung Ho 
Published: September 2022

AbstractPreviously, we showed that Trp-Lys-Tyr-Met-Val-d-Met(WKYMVm) stimulates superoxide generation and chemotactic migration inmonocytes and neutrophils. In this study, we examined the effect of WKYMVm on monocyte survival. Serum starvation-induced monocyte deathwas attenuated in the presence of WKYMVm, which was abated when thecells were preincubated with LY294002, suggesting the involvement of phosphoinositide-3-kinase (PI 3-kinase) in the peptide-induced monocytesurvival. WKYMVm stimulated ERK and Akt activity via PI 3-kinaseactivation in monocytes. We also investigated the signaling pathway of WKYMVm-induced ERK and Akt activation. The WKYMVm-induced ERKactivation was PI 3-kinase-dependent but PKC-independent. However, Aktactivation by WKYMVm was dependent not only on PI 3-kinase but also onthe PKC pathway. When monocytes were incubated with WKYMVm, caspase-3activity, which is important for cell death, was inhibited. Pretreatment of the cells with LY294002, GF109203X, and Go 6976 but notPD98059 blocked WKYMVm-induced monocyte survival and caspase-3inhibition. In summary, the novel chemoattractant WKYMVm enhancesmonocyte survival via Akt-mediated pathways, and in this process, PKCand PI 3-kinase act upstream of Akt.
The role of PPARs in inflammation and immunity
Authors: Clark Robert B 
Published: September 2022

AbstractThe family of transcription factors termed peroxisome proliferator-activated receptors (PPARs) has recently been the focus of much interest for their possible role in the regulation of inflammation and immune responses. PPARα and PPARγ have been implicated in the regulation of macrophage and endothelial cell inflammatory responses. Although PPAR activation has generally been shown to have anti-inflammatory effects, opposite effects have been noted, and results often appear to depend on the ligands being used and the inflammatory parameters being measured. Recently, my laboratory and others have described a role for PPARγ in the responses of T lymphocytes. Ligands for PPARγ have been found to inhibit proliferation of activated T cells, and this appears to involve inhibition of IL-2 secretion and/or the induction of apoptosis. However, one problem in the interpretation of many of the studies of PPARγ, inflammation, and immunity is that ligands thought to be specific for PPARγ may have regulatory effects on inflammatory parameters that are PPARγ-independent. Future studies of the role of the PPARs in inflammatory and immune responses should include further studies of T cells, T-cell subsets, and dendritic cells but will have to re-examine the issue of PPAR specificity of the ligands being used. This may require further knockout studies and technology, together with the identification of endogenous and perhaps more specific synthetic PPAR ligands.
Toll-like receptor 2 (TLR2) mediates activation of stress-activated MAP kinase p38
Authors: Vasselon Thierry , Hanlon William A , Wright Samuel D , Detmers Patricia A 
Published: September 2022

AbstractEarly events in the response of cells to lipopolysaccharide (LPS) include activation of NF-κB and stress-activated MAP kinase p38. Recent studies have shown that the human Toll-like receptor 2 (TLR2) mediates activation of NF-κB in response to commercial preparations of LPS (comLPS), membrane lipoproteins, and Gram-positive bacterial products. Here, we show that expression of TLR2 in human embryonic kidney 293 cells enabled p38 phosphorylation in response to comLPS, a synthetic bacterial lipoprotein, and B. subtilis. Activation of p38 was confirmed by an in vitro kinase assay using ATF2 as substrate and by an assay measuring activation of the downstream effector of p38, MAP kinase-activated protein kinase in cells. Thus, TLR2 initiated the signaling pathway for p38 in response to bacterial products.
A novel phenotype for an activated macrophage: the type 2 activated macrophage
Authors: Anderson Charles F , Mosser David M 
Published: September 2022

AbstractActivated macrophages were used as antigen presenting cells (APCs) to determine the extent to which these APCs could influence an adaptive immune response. We show that activated macrophages induced a strong polarized Th1-like T cell response that was predominated by IFN-γ. However, when antigen was targeted to Fcγ receptors on these macrophages, their phenotype changed, and they now induced a T cell response that was predominated by IL-4. The initial biasing by activated macrophages toward a Th1-like response was a result of activation of the innate immune response, as macrophages from MyD88−/− mice failed to produce Th1-inducing cytokines. The reversal of the Th1 biasing was a result of FcγR ligation, as macrophages lacking the FcR common γ chain failed to reverse this biasing. To show that this biasing could occur in vivo, mice were injected with activated macrophages or activated macrophages whose FcγR had been ligated with an irrelevant immune complex. Mice injected with FcγR-ligated macrophages made more antibody than those receiving conventionally activated macrophages, and the antibody was predominantly of the IgG1 isotype. These studies demonstrate that FcγR ligation on activated macrophages can change the phenotype of these APCs to cells that preferentially drive a Th2-like response. We have termed these cells type 2 activated macrophages.
TGF-β1 and IFN-γ cross-regulate antigen presentation to CD4 T cells by macrophages
Authors: Delvig Alexei A , Lee Jeong J , Chrzanowska-Lightowlers Zosia M A , Robinson John H 
Published: September 2022

AbstractWe studied the interaction of transforming growth factor-β1 (TGF-β1) and interferon-γ (IFN-γ) in regulating Ag presentation in macrophages. TGF-β1 blocked, and IFN-γ enhanced Ag presentation of two T cell epitopes from the group A streptococcal M protein processed from viable Streptococcus pyogenes. Consistent with the functional data, TGF-β1 reduced the constitutive expression of MHC class II transactivator (CIITA), MHC class II (MHC-II), invariant chain, and DO mRNA, whereas IFN-γ up-regulated the expression of CIITA and MHC-II mRNA without affecting invariant chain or DO mRNA. However, neither cytokine affected DM mRNA expression. Treatment of macrophages with the two cytokines in combination showed that TGF-β1 down-regulated IFN-γ-mediated enhancement of antigen presentation and inhibited IFN-γ-inducible CIITA and MHC-II class II mRNA expression. The effect of TGF-β1 on Ag presentation was shown to be independent of the surface expression of CD80, CD86, or CD40 costimulatory molecules by flow cytometry. Our results show that TGF-β1 and IFN-γ cross-regulate Ag presentation by influencing the transcription of several genes associated with antigen presentation function, which may represent an important mechanism limiting T cell activation during an immune response.
Modulation of malignant B cell activation and apoptosis by bcl-2 antisense ODN and immunostimulatory CpG ODN
Authors: Jahrsdörfer B , Jox R , Mühlenhoff L , Tschoep K , Krug A , Rothenfusser S , Meinhardt G , Emmerich B , Endres S , Hartmann G 
Published: September 2022

AbstractInhibition of bcl-2 expression by antisense oligodeoxynucleotides (ODN) might render bcl-2 overexpressing malignant B cells more susceptible to chemotherapy. ODN containing unmethylated CG dinucleotides (CpG) are known to activate B cells. We studied the effects of two bcl-2 antisense ODN, with (G3139) or without CG dinucleotides (NOV 2009) within the sequence, and the effects of a nonantisense, CpG-containing ODN (ODN 2006) on activation and apoptosis of malignant B cell lines and primary B-CLL cells. Without cationic lipids, no antisense-mediated inhibition of bcl-2 synthesis was achieved with G3139 and NOV 2009. Instead, G3139, but not NOV 2009, induced similar changes as ODN 2006 in proliferation, expression of costimulatory and antigen-presenting molecules, as well as in bcl-2 and bcl-xL levels of primary B-CLL cells. G3139 and ODN 2006 inhibited in vitro, spontaneous apoptosis in B-CLL cells of patients with high serum thymidine kinase activity (s-TK, marker for proliferative activity of malignant B cells), whereas in patients with low s-TK activity, apoptosis was induced. In conclusion, our results suggest that modulation of malignant B cell apoptosis by G3139 depends on its immunostimulatory properties rather than on antisense-mediated reduction of bcl-2 expression. Immunostimulatory CpG ODN may have a therapeutic potential in patients with B-CLL, especially those with low s-TK activity.
Role of CXCL1 in tumorigenesis of melanoma
Authors: Dhawan Punita , Richmond Ann 
Published: September 2022

AbstractThe CXC chemokine, CXCL1 (melanoma growth-stimulatory activity/growth-regulated protein α), plays a major role in inflammation, angiogenesis, tumorigenesis, and wound healing. Recently, chemokines have been extensively related to cellular transformation, tumor growth, homing, and metastasis. CXCL1 and its mouse homologue MIP-2 have been shown to be involved in the process of tumor formation. When chemokines such as CXCL1 and CXCL8 (IL-8) become disregulated so that they are chronically expressed, tissue damage, angiogenesis, and tumorigenesis can follow. This up-regulation of chemokines has been attributed to constitutive activation of NF-κB. The constitutive NF-κB activation is an emerging hallmark in various types of tumors including breast, colon, pancreatic, ovarian, as well as melanoma. Previous findings from our laboratory and other laboratories have demonstrated the role of endogenous activation of NF-κB in association with enhanced metastatic potential of malignant melanoma cells and suggest that targeting NF-κB may have potential therapeutic effects in clinical trials. An important step in this direction would be to delineate the important intracellular pathways and upstream kinases involved in up-regulation of NF-κB in melanoma cells. In this review, the signaling pathways involved in the disregulation of NF-κB and chemokine expression are discussed.
Complement's participation in acquired immunity
Authors: Nielsen Claus Henrik , Leslie Robert Graham Quinton 
Published: September 2022

AbstractThe preliminary evidence for the involvement of complement in promoting primary humoral responses dates back over a quarter of a century. However, it is only in the course of the past decade or so that the detailed mechanisms underlying complement's influence have been characterized in depth. It is now clear that complement serves as a regulator of several B cell functions, including specific antibody production, antigen uptake, processing and presentation, and shaping of the B cell repertoire. Of key importance, in this respect, is the role played by the B cell-signaling triad consisting of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcγRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses.
CD4 lymphocytes in the blood of HIV+ individuals migrate rapidly to lymph nodes and bone marrow: support for homing theory of CD4 cell depletion
Authors: Chen Jenny J-Y , Huang Jason C , Shirtliff Mark , Briscoe Elma , Ali Seham , Cesani Fernando , Paar David , Cloyd Miles W 
Published: September 2022

AbstractThe mechanism(s) by which human immunodeficiency virus (HIV) causes depletion of CD4 lymphocytes remains unknown. Evidence has been reported for a mechanism involving HIV binding to (and signaling) resting CD4 lymphocytes in lymphoid tissues, resulting in up-regulation of lymph node homing receptors and enhanced homing after these cells enter the blood, and induction of apoptosis in many of these cells during the homing process, caused by secondary signaling through homing receptors. Supportive evidence for this as a major pathogenic mechanism requires demonstration that CD4 lymphocytes in HIV+ individuals do migrate to lymph nodes at enhanced rates. Studies herein show that freshly isolated CD4 lymphocytes labeled with 111Indium and intravenously reinfused back into HIV+ human donors do home to peripheral lymph nodes at rates two times faster than normal. They also home at enhanced rates to iliac and vertebral bone marrow. In contrast, two hepatitis B virus-infected subjects displayed less than normal rates of blood CD4 lymphocyte migration to peripheral lymph nodes and bone marrow. Furthermore, the increased CD4 lymphocyte homing rates in HIV+ subjects returned to normal levels after effective, highly active antiretroviral therapy treatment, showing that the enhanced homing correlated with active HIV replication. This is the first direct demonstration of where and how fast CD4 lymphocytes in the blood traffic to tissues in normal and HIV-infected humans. The results support the theory that the disappearance of CD4 lymphocytes from the blood of HIV+ patients is a result of their enhanced migration out of the blood (homing) and dying in extravascular tissues.
The viral manipulation of the host cellular and immune environments to enhance propagation and survival: a focus on RNA viruses
Authors: Mahalingam Surendran , Meanger Jayesh , Foster Paul S , Lidbury Brett A 
Published: September 2022

AbstractVirus infection presents a significant challenge to host survival. The capacity of the virus to replicate and persist in the host is dependent on the status of the host antiviral defense mechanisms. The study of antiviral immunity has revealed efective antiviral host immune responses and enhanced our knowledge of the diversity of viral immunomodulatory strategies that undermine these defences. This review describes the diverse approaches that are used by RNA viruses to trick or evade immune detection and response systems. Some of these approaches include the specific targeting of the major histocompatibility complex-restricted antigen presentation pathways, apoptosis, disruption of cytokine function and signaling, exploitation of the chemokine system, and interference with humoral immune responses. A detailed insight into interactions of viruses with the immune system may provide direction in the development of new vaccine strategies and novel antiviral compounds.
Interferon-γ stimulates the expression of galectin-9 in cultured human endothelial cells
Authors: Imaizumi Tadaatsu , Kumagai Mika , Sasaki Naoko , Kurotaki Hidekachi , Mori Fumiaki , Seki Masako , Nishi Nozomu , Fujimoto Koji , Tanji Kunikazu , Shibata Takeo , Tamo Wakako , Matsumiya Tomoh , Yoshida Hidemi , Cui Xue-Fan , Takanashi Shingo , Hanada Katsumi , Okumura Ken , Yagihashi Soroku , Wakabayashi Koichi , Nakamura Takanori , Hirashima Mitsuomi , Satoh Kei 
Published: September 2022

AbstractGalectin-9 is a member of the galectin family and has been identified as an eosinophil chemoattractant produced by activated T lymphocytes. Vascular endothelial cells play an important role in the initial step of eosinophil recruitment and activation in immune and inflammatory responses. We have addressed the stimulation of galectin-9 expression in endothelial cells. Galectin-9 was detected in membrane and cytosolic fractions of human umbilical vein endothelial cells stimulated with interferon-γ (IFN-γ). IFN-γ also enhanced the adhesion of human eosinophilic leukemia-1 cells to endothelial monolayers, and it was inhibited by the presence of lactose. Interleukin-4, which induces eotaxin expression, did not affect the expression of galectin-9. The in situ endothelium from patients with inflammatory diseases was found to express galectin-9. IFN-γ-induced production of galectin-9 by endothelial cells may play an important role in immune responses by regulating interactions between the vascular wall and eosinophils.
Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2) throughout maturation
Authors: Yang De , Chen Qian , Gertz Barry , He Rong , Phulsuksombati Michele , Ye Richard D , Oppenheim Joost J 
Published: September 2022

AbstractImmature and mature dendritic cells (iDC and mDC, respectively) migrate to different anatomical sites, e.g., sites of antigen (Ag) deposition and secondary lymphoid organs, respectively, to fulfill their roles in the induction of primary, Ag-specific immune responses. The trafficking pattern of iDC andmDC is based on their expression of functional chemotactic receptors and the in vivo sites expressing the corresponding ligands including chemokines and/or classical chemoattractants. In this study, we have evaluated the expression of the formyl peptide receptor like-2 (FPRL2) by human iDC and mDC. We show that iDC respond chemotactically and by Ca2+ mobilization to N-formyl-Met-Leu-Phe and a recently identified synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), whereas mDC derived from the same donor only respond to WKYMVm. Furthermore, iDC and mDC express FPRL2 mRNA and protein. As mDC do not express any other members of the human FPR subfamily, FPRL2 expressed by DC must be functional and mediate the effect of WKYMVm on DC. Indeed, treatment of iDC and mDC with WKYMVm induces the internalization of FPRL2. Thus, human myeloid DC express functional FPRL2 and maintain its expression even after maturation, suggesting that the interaction of FPRL2 and its endogenous ligand(s) may be involved in regulating DC trafficking during Ag uptake and processing in the periphery as well as the T cell-stimulating phase of the immune responses.
Experimental basis of hematopoietic stem cell transplantation for treatment of autoimmune diseases
Authors: van Bekkum D W 
Published: September 2022

AbstractExperiments with animal models of autoimmune disease provided the rational and stimulus for the current, clinical studies of autologous stem cell transplantation for the treatment of a variety of severe, refractory, autoimmune diseases. The discoveries that led to the recognition of the key role of hematopoietic stem cells and the successful treatment of autoimmune diseases with bone marrow transplants are reviewed. The relevance of spontaneous and induced autoimmune disease models for the development of clinical treatment regimens is discussed. Most of the investigations with autologous stem cell transplantation have been performed with induced autoimmune disorders: in rats with adjuvant arthritis and in rats or mice with experimental, allergic encephalomyelitis, the current model for multiple sclerosis. The main aspects of this translational research were the conditioning regimens and the degree of T cell depletion of the graft as determinants of remission induction and the incidence of relapses. The emerging recommendations are compared with the outcome so far of the clinical studies.