-
Redox Report : Communications in Free... Jul 2015Prolidase plays a major role in collagen turnover, matrix remodeling, and cell growth. Benign prostatic hyperplasia (BPH) may be associated with an increased...
OBJECTIVES
Prolidase plays a major role in collagen turnover, matrix remodeling, and cell growth. Benign prostatic hyperplasia (BPH) may be associated with an increased extracellular matrix deposition. Therefore, the present study was designed to investigate the plasma prolidase activity, oxidative status, and peripheral mononuclear leukocyte DNA damage in patients with BPH.
PATIENTS AND METHODS
Twenty-six male patients with BPH and 24 healthy male subjects were included in this study. Blood samples were collected from antecubital vein after an overnight fasting period, and the plasma was separated. Plasma prolidase activity, total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were determined. The peripheral lymphocyte oxidative DNA damage was determined using an alkaline single cell gel electrophoresis assay (comet assay).
RESULTS
The plasma prolidase activity, TOS levels, OSI values, and peripheral mononuclear leukocyte DNA damage were significantly higher (P < 0.001), while the TAC levels were significantly lower (P < 0.001) in patients with BPH than controls. In BPH patients, the prolidase activity was significantly associated with TAC levels (r = -0.366, P < 0.05), TOS levels (r = 0.573, P < 0.001), and OSI (r = 0.618, P < 0.001) and peripheral mononuclear leukocyte DNA damage (r = 0.461, P < 0.001).
CONCLUSIONS
Our results showed that BPH might be associated with an increased oxidative stress, and also an increased plasma prolidase activity. Increased prolidase activity might play an important role in the etiopathogenesis and/or progression of BPH.
Topics: Antioxidants; Collagen; Comet Assay; DNA Damage; Dipeptidases; Extracellular Matrix; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Oxidants; Oxidative Stress; Prospective Studies; Prostatic Hyperplasia
PubMed: 25551736
DOI: 10.1179/1351000214Y.0000000121 -
Microscopy Research and Technique Jan 2018This article studies the morphological and mechanical features of multinuclear and mononuclear SW480 colon cancer cells by atomic force microscopy to understand their...
This article studies the morphological and mechanical features of multinuclear and mononuclear SW480 colon cancer cells by atomic force microscopy to understand their drug-resistance. The SW480 cells were incubated with the fullerenol concentrations of 1 mg/ml and 2 mg/ml. Morphological and mechanical features including the height, length, width, roughness, adhesion force and Young's modulus of three multinuclear cell groups and three mononuclear cell groups were imaged and analyzed. It was observed that the features of multinuclear cancer cells and mononuclear cancer cells were significantly different after the treatment with fullerenol. The experiment results indicated that the mononuclear SW480 cells were more sensitive to fullerenol than the multinuclear SW480 cells, and the multinuclear SW480 cells exhibited a stronger drug-resistance than the mononuclear SW480 cells. This work provides a guideline for the treatments of multinuclear and mononuclear cancer cells with drugs.
Topics: Antineoplastic Agents; Biomechanical Phenomena; Cell Line, Tumor; Colonic Neoplasms; Elastic Modulus; Fullerenes; Giant Cells; Humans; Leukocytes, Mononuclear; Microscopy, Atomic Force
PubMed: 28990709
DOI: 10.1002/jemt.22950 -
Clinical and Experimental Immunology Dec 2023Esophageal squamous cell carcinoma (ESCC), one of the most commonly diagnosed and lethal malignant diseases, has a complex tumor ecosystem. An obvious requirement for...
Esophageal squamous cell carcinoma (ESCC), one of the most commonly diagnosed and lethal malignant diseases, has a complex tumor ecosystem. An obvious requirement for T-cell-mediated tumor control is the infiltration of tumor-reactive T cells into the tumor. Here, we obtained detailed T-cell compositions in both ESCC tumors and matched peripheral blood mononuclear cells (PBMCs) at single-cell resolution. We demonstrated that T cells in tumors and PBMCs had different compositions and functional states. ESCC tumors were rich in Treg and exhausted T cells but poor in cytotoxic and naïve T cells compared with PBMCs. The exhausted T cells showed higher exhausted signature in tumors than in PBMCs, while the cytotoxic T cells exhibited higher cytotoxic signature in PBMCs than in tumors. Our data indicated an immunosuppressive status and a defect at the level of T-cell priming in the tumor microenvironment. Leukocyte-associated Ig-like receptor-2 (LAIR2), a soluble collagen receptor that prevents the binding of human leukocyte-associated Ig-like receptor-1 (LAIR1) to collagens, was predominantly expressed in proliferating CD8+ T and Treg cells in tumors but in cytotoxic cells in PBMCs. LAIR2 could inhibit tumor metastasis, invasion, and collagen deposition via suppressing transforming growth factor-β signaling. These findings revealed differential T-cell populations in tumors and PBMCs and provided convincing evidence that LAIR2 acted as a tumor suppressor.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Leukocytes, Mononuclear; Ecosystem; T-Lymphocytes, Regulatory; Tumor Microenvironment
PubMed: 37422711
DOI: 10.1093/cei/uxad073 -
Cytometry. Part a : the Journal of the... Jun 2018
Review
Topics: B-Lymphocytes; Flow Cytometry; Humans; Leukocytes, Mononuclear; Membrane Glycoproteins; Phenotype
PubMed: 29782066
DOI: 10.1002/cyto.a.23488 -
Scientific Reports Nov 2021Fibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). These cells have...
Fibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). These cells have primarily been characterized in the RA synovial membrane. Here we aim to phenotypically and functionally characterize cultured synovial fluid-derived FLS (sfRA-FLS). Paired peripheral blood mononuclear cells (PBMC) and sfRA-FLS from patients with RA were obtained and monocultures of sfRA-FLS and autologous co-cultures of sfRA-FLS and PBMC were established. The in situ activated sfRA-FLS were CD34-, CD45-, Podoplanin+, Thymocyte differentiation antigen-1+. SfRA-FLS expressed uniform levels of NFкB-related pathway proteins and secreted several pro-inflammatory cytokines dominated by IL-6 and MCP-1. In a co-culture model with autologous PBMC, the ICAM-1 and HLA-DR expression on sfRA-FLS and secretion of IL-1β, IL-6, and MCP-1 increased. In vivo, human sfRA-FLS were cartilage invasive both at ipsilateral and contralateral implantation site. We conclude that, sfRA-FLS closely resemble the pathological sublining layer FLS subset in terms of surface protein expression, cytokine production and leukocyte cross-talk potential. Further, sfRA-FLS are comparable to tissue-derived FLS in their capabilities to invade cartilage at implantation sites but also spread tissue destruction to a distant site. Collectively, sfRA-FLS can serve as a an easy-to-obtain source of pathological sublining FLS in RA.
Topics: Arthritis, Rheumatoid; Biomarkers; Cell Line; Cells, Cultured; Cytokines; Disease Progression; Disease Susceptibility; Fibroblasts; Humans; Immunophenotyping; Inflammation Mediators; Leukocytes, Mononuclear; Phenotype; Synovial Fluid; Synoviocytes
PubMed: 34772990
DOI: 10.1038/s41598-021-01692-7 -
Nutrients Feb 2021The dietary isothiocyanate L-sulforaphane (LSF), derived from cruciferous vegetables, is reported to have several beneficial biological properties, including...
The dietary isothiocyanate L-sulforaphane (LSF), derived from cruciferous vegetables, is reported to have several beneficial biological properties, including anti-inflammatory and immunomodulatory effects. However, there is limited data on how LSF modulates these effects in human immune cells. The present study was designed to investigate the immunomodulatory effects of LSF (10 µM and 50 µM) on peripheral blood mononuclear cell (PBMC) populations and cytokine secretion in healthy adult volunteers ( = 14), in the presence or absence of bacterial (lipopolysaccharide) and viral (imiquimod) toll-like receptor (TLRs) stimulations. Here, we found that LSF reduced pro-inflammatory cytokines interleukin (IL)-6, IL-1β, and chemokines monocyte chemoattractant protein (MCP)-1 irrespective of TLR stimulations. This result was associated with LSF significantly reducing the proportion of natural killer (NK) cells and monocytes while increasing the proportions of dendritic cells (DCs), T cells and B cells. We found a novel effect of LSF in relation to reducing cluster of differentiation (CD) 14 monocytes while simultaneously increasing monocyte-derived DCs (moDCs: lineage-Human Leukocyte Antigen-DR isotype (HLA-DR)CD11b CD11c). LSF was also shown to induce a 3.9-fold increase in the antioxidant response element (ARE) activity in a human monocyte cell line (THP-1). Our results provide important insights into the immunomodulatory effects of LSF, showing in human PBMCs an ability to drive differentiation of monocytes towards an immature monocyte-derived dendritic cell phenotype with potentially important biological functions. These findings provide insights into the potential role of LSF as a novel immunomodulatory drug candidate and supports the need for further preclinical and phase I clinical studies.
Topics: Adult; Bodily Secretions; Cell Differentiation; Cell Line; Cytokines; Dendritic Cells; Female; Healthy Volunteers; Humans; Immunologic Factors; Immunomodulation; Isothiocyanates; Killer Cells, Natural; Leukocytes, Mononuclear; Male; Sulfoxides
PubMed: 33673203
DOI: 10.3390/nu13020602 -
Stem Cell Reports Apr 2021ESC- and iPSC-derived retinal transplantation is a promising therapeutic approach for disease with end-stage retinal degeneration, such as retinitis pigmentosa and...
ESC- and iPSC-derived retinal transplantation is a promising therapeutic approach for disease with end-stage retinal degeneration, such as retinitis pigmentosa and age-related macular degeneration. We previously showed medium- to long-term survival, maturation, and light response of transplanted human ESC- and iPSC-retina in mouse, rat, and monkey models of end-stage retinal degeneration. Because the use of patient hiPSC-derived retina with a disease-causing gene mutation is not appropriate for therapeutic use, allogeneic transplantation using retinal tissue/cells differentiated from a stocked hESC and iPSC line would be most practical. Here, we characterize the immunological properties of hESC- and iPSC-retina and present their three major advantages: (1) hESC- and iPSC-retina expressed low levels of human leukocyte antigen (HLA) class I and little HLA class II in vitro, (2) hESC- and iPSC-retina greatly suppressed immune activation of lymphocytes in co-culture, and (3) hESC- and iPSC-retina suppressed activated immune cells partially via transforming growth factor β signaling. These results support the use of allogeneic hESC- and iPSC-retina in future clinical application.
Topics: Animals; Cell Differentiation; Histocompatibility Antigens Class I; Human Embryonic Stem Cells; Humans; Immunomodulation; Immunosuppression Therapy; Induced Pluripotent Stem Cells; Interferon-gamma; Leukocytes, Mononuclear; Primates; Recombinant Proteins; Retina; Retinal Pigment Epithelium; Transforming Growth Factor beta
PubMed: 33770500
DOI: 10.1016/j.stemcr.2021.02.021 -
Genes Jun 2020The view of the nucleolus as a mere ribosomal factory has been recently expanded, highlighting its essential role in immune and stress-related signalling and...
The view of the nucleolus as a mere ribosomal factory has been recently expanded, highlighting its essential role in immune and stress-related signalling and orchestrating. It has been shown that the nucleolus structure, formed around nucleolus organiser regions (NORs) and attributed Cajal bodies, is prone to disassembly and reassembly correlated to various physiological and pathological stimuli. To evaluate the effect of parasite stimulus on the structure of the leukocyte nucleolus, we exposed rat peripheral blood mononuclear cells (PBMC) to the crude extract of the nematode (Anisakidae), and compared the observed changes to the effect of control (RPMI-1640 media), immunosuppressive (MPA) and immunostimulant treatment (bacterial lipopolysaccharide (LPS) and viral analogue polyinosinic:polycytidylic acid (poly I:C)) by confocal microscopy. Poly I:C triggered the most accentuated changes such as nucleolar fragmentation and structural unravelling, LPS induced nucleolus thickening reminiscent of cell activation, while MPA induced disassembly of dense fibrillar and granular components. crude extract triggered nucleolar segregation, expectedly more enhanced in treatment with a higher dose. This is the first evidence that leukocyte nucleoli already undergo structural changes 12 h post-parasitic stimuli, although these are likely to subside after successful cell activation.
Topics: Animals; Anisakiasis; Anisakis; Cell Nucleolus; Humans; Immunosuppressive Agents; Interstitial Cells of Cajal; Leukocytes; Leukocytes, Mononuclear; Lipopolysaccharides; Nucleolus Organizer Region; Poly I-C
PubMed: 32585969
DOI: 10.3390/genes11060688 -
Scientific Reports Mar 2021Natural Killer (NK) cells acquire memory-like properties following a brief stimulation with IL-12, IL-15 and IL-18. These IL-12/15/18-preactivated NK cells, also known...
Natural Killer (NK) cells acquire memory-like properties following a brief stimulation with IL-12, IL-15 and IL-18. These IL-12/15/18-preactivated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have been revealed as a powerful tool in cancer immunotherapy due to their persistence in the host and their increased effector functions. Several studies have shown that NK cells modulate their metabolism in response to cytokine-stimulation and other stimuli, suggesting that there is a link between metabolism and cellular functions. In this paper, we have analyzed metabolic changes associated to IL-12/15/18-stimulation and the relevance of glycolytic pathway for NK cell effector functions. We have found CIML NK cells are able to retain a metabolic profile shifted towards glycolysis seven days after cytokine withdrawal. Furthermore, we found that treatment with 2-DG differently affects distinct NK cell effector functions and is stimuli-dependent. These findings may have implications in the design of NK cell-based cancer immunotherapies.
Topics: Cells, Cultured; Glycolysis; Humans; Interleukins; K562 Cells; Killer Cells, Natural; Leukocytes, Mononuclear; Metabolome
PubMed: 33742092
DOI: 10.1038/s41598-021-85960-6 -
Gene Therapy Apr 2023A primary goal in transplantation medicine is the induction of a tolerogenic environment for prevention of transplant rejection without the need for long-term...
A primary goal in transplantation medicine is the induction of a tolerogenic environment for prevention of transplant rejection without the need for long-term pharmacological immunosuppression. Generation of alloantigen-specific regulatory T cells (Tregs) by transduction with chimeric antigen receptors (CARs) is a promising strategy to achieve this goal. This publication reports the preclinical characterization of Tregs (TR101) transduced with a human leukocyte antigen (HLA)-A*02 CAR lentiviral vector (TX200) designated to induce immunosuppression of allograft-specific effector T cells in HLA-A*02-negative recipients of HLA-A*02-positive transplants. In vitro results demonstrated specificity, immunosuppressive function, and safety of TX200-TR101. In NOD scid gamma (NSG) mice, TX200-TR101 prevented graft-versus-host disease (GvHD) in a xenogeneic GvHD model and TX200-TR101 Tregs localized to human HLA-A*02-positive skin transplants in a transplant model. TX200-TR101 persisted over the entire duration of a 3-month study in humanized HLA-A*02 NSG mice and remained stable, without switching to a proinflammatory phenotype. Concomitant tacrolimus did not impair TX200-TR101 Treg survival or their ability to inhibit peripheral blood mononuclear cell (PBMC) engraftment. These data demonstrate that TX200-TR101 is specific, stable, efficacious, and safe in preclinical models, and provide the basis for a first-in-human study.
Topics: Mice; Animals; Humans; Receptors, Chimeric Antigen; T-Lymphocytes, Regulatory; Leukocytes, Mononuclear; Graft vs Host Disease; Organ Transplantation; HLA-A Antigens
PubMed: 35931871
DOI: 10.1038/s41434-022-00358-x