scholarly journals Oxalate Alters Cellular Bioenergetics, Redox Homeostasis, Antibacterial Response, and Immune Response in Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Parveen Kumar ◽  
Kanchan Saini ◽  
Vikram Saini ◽  
Tanecia Mitchell
Keyword(s):  
Immune Response ◽  
Calcium Oxalate ◽  
Inflammatory Cytokine ◽  
Redox Homeostasis ◽  
Critical Role ◽  
Immune Defense ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
Bacterial Response ◽  
Cellular Bioenergetics

Individuals with calcium oxalate (CaOx) kidney stones can have secondarily infected calculi which may play a role in the development of recurrent urinary tract infection (UTI). Uropathogenic Escherichia coli (UPEC) is the most common causative pathogen of UTIs. Macrophages play a critical role in host immune defense against bacterial infections. Our previous study demonstrated that oxalate, an important component of the most common type of kidney stone, impairs monocyte cellular bioenergetics and redox homeostasis. The objective of this study was to investigate whether oxalate compromises macrophage metabolism, redox status, anti-bacterial response, and immune response. Monocytes (THP-1, a human monocytic cell line) were exposed to sodium oxalate (soluble oxalate; 50 µM) for 48 hours prior to being differentiated into macrophages. Macrophages were subsequently exposed to calcium oxalate crystals (50 µM) for 48 hours followed by UPEC (MOI 1:2 or 1:5) for 2 hours. Peritoneal macrophages and bone marrow-derived macrophages (BMDM) from C57BL/6 mice were also exposed to oxalate. THP-1 macrophages treated with oxalate had decreased cellular bioenergetics, mitochondrial complex I and IV activity, and ATP levels compared to control cells. In addition, these cells had a significant increase in mitochondrial and total reactive oxygen species levels, mitochondrial gene expression, and pro-inflammatory cytokine (i.e. Interleukin-1β, IL-1β and Interleukin-6, IL-6) mRNA levels and secretion. In contrast, oxalate significantly decreased the mRNA levels and secretion of the anti-inflammatory cytokine, Interleukin-10 (IL-10). Further, oxalate increased the bacterial burden of primary macrophages. Our findings demonstrate that oxalate compromises macrophage metabolism, redox homeostasis, and cytokine signaling leading to a reduction in anti-bacterial response and increased infection. These data highlight a novel role of oxalate on macrophage function.

scholarly journals IL-12 Inhibits Lipopolysaccharide Stimulated Osteoclastogenesis in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Masako Yoshimatsu ◽  
Hideki Kitaura ◽  
Yuji Fujimura ◽  
Haruka Kohara ◽  
Yukiko Morita ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Bone Resorption ◽  
Host Defense ◽  
Inflammatory Cytokine ◽  
Mrna Level ◽  
Critical Role ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Resorption Marker ◽  
Mrna Levels ◽  
Tracp 5B

Lipopolysaccharide (LPS) is related to osteoclastogenesis in osteolytic diseases. Interleukin- (IL-) 12 is an inflammatory cytokine that plays a critical role in host defense. In this study, we investigated the effects of IL-12 on LPS-induced osteoclastogenesis. LPS was administered with or without IL-12 into the supracalvariae of mice, and alterations in the calvarial suture were evaluated histochemically. The number of osteoclasts in the calvarial suture and the mRNA level of tartrate-resistant acid phosphatase (TRAP), an osteoclast marker, were lower in mice administered LPS with IL-12 than in mice administered LPS alone. The serum level of tartrate-resistant acid phosphatase 5b (TRACP 5b), a bone resorption marker, was also lower in mice administered LPS with IL-12 than in mice administered LPS alone. These results revealed that IL-12 might inhibit LPS-induced osteoclastogenesis and bone resorption. In TdT-mediated dUTP-biotin nick end-labeling (TUNEL) assays, apoptotic changes in cells were recognized in the calvarial suture in mice administered LPS with IL-12. Furthermore, the mRNA levels of both Fas and FasL were increased in mice administered LPS with IL-12. Taken together, the findings demonstrate that LPS-induced osteoclastogenesis is inhibited by IL-12 and that this might arise through apoptotic changes in osteoclastogenesis-related cells induced by Fas/FasL interactions.

scholarly journals Importance of IL-10 Modulation by Probiotic Microorganisms in Gastrointestinal Inflammatory Diseases

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Alejandra de Moreno de LeBlanc ◽  
Silvina del Carmen ◽  
Meritxell Zurita-Turk ◽  
Clarissa Santos Rocha ◽  
Maarten van de Guchte ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokine ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Genetically Engineered ◽  
Wide Range ◽  
Prevention And Treatment ◽  
Therapeutic Properties ◽  
Anti Inflammatory Cytokine

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods and possess a wide range of therapeutic properties. The aim of this paper is to present an overview of the current expanding knowledge of one of the mechanisms by which LAB and other probiotic microorganisms participate in the prevention and treatment of gastrointestinal inflammatory disease through their immune-modulating properties. A special emphasis will be placed on the critical role of the anti-inflammatory cytokine IL-10, and a brief overview of the uses of genetically engineered LAB that produce this important immune response mediator will also be discussed. Thus, this paper will demonstrate the critical role that IL-10 plays in gastrointestinal inflammatory diseases and how probiotics could be used in their treatment.

scholarly journals Genetic Deletion of Murine SPRY Domain-Containing SOCS Box Protein 2 (SSB-2) Results in Very Mild Thrombocytopenia

2005 ◽  
Vol 25 (13) ◽  
pp. 5639-5647 ◽  
Author(s):  
S. L. Masters ◽  
K. R. Palmer ◽  
W. S. Stevenson ◽  
D. Metcalf ◽  
E. M. Viney ◽  
...  
Keyword(s):  
Hematological Parameters ◽  
Mammalian Species ◽  
Critical Role ◽  
Physiological Role ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
Homologous Proteins ◽  
Platelet Production ◽  
Spry Domain ◽  
Socs Box

ABSTRACT The SSB family is comprised of four highly homologous proteins containing a C-terminal SOCS box motif and a central SPRY domain. No function has yet been ascribed to any member of this family in mammalian species despite a clear role for other SOCS proteins in negative regulation of cytokine signaling. To investigate its physiological role, the murine Ssb-2 gene was deleted by homologous recombination. SSB-2-deficient mice were shown to have a reduced rate of platelet production, resulting in very mild thrombocytopenia (25% decrease in circulating platelets). Tissue histology and other hematological parameters were normal, as was the majority of serum biochemistry, with the exception that blood urea nitrogen (BUN) levels were decreased in mice lacking SSB-2. Quantitative analysis of SSB mRNA levels indicated that SSB-1, -2, and -3 were ubiquitously expressed; however, SSB-4 was only expressed at very low levels. SSB-2 expression was observed in the kidney and in megakaryocytes, a finding consistent with the phenotype of mice lacking this gene. Deletion of SSB-2 thus perturbs the steady-state level of two tightly controlled homeostatic parameters and identifies a critical role for SSB-2 in regulating platelet production and BUN levels.

scholarly journals Role of SOCS2 in the Regulation of Immune Response and Development of the Experimental Autoimmune Encephalomyelitis

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Allysson Cramer ◽  
Bruno Cabral de Lima Oliveira ◽  
Paulo Gaio Leite ◽  
David Henrique Rodrigues ◽  
Fatima Brant ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Immune Response ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Acute Phase ◽  
Critical Role ◽  
Recovery Phase ◽  
Cytokine Signaling ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Experimental Autoimmune Encephalomyelitis (EAE) is the most widely used animal model for the study of MS. The Suppressor of Cytokine Signaling (SOCS) 2 protein plays a critical role in regulating the immune responses. The role of SOCS2 during EAE has not been explored. EAE was induced in WT and SOCS2-/- mice using myelin oligodendrocyte glycoprotein (MOG35-55) peptide. Brain and spinal cord were examined during the peak (day 14) and recovery phase (day 28) of the disease. SOCS2 was upregulated in the brain of WT mice at the peak and recovery phase of EAE. The development of the acute phase was slower in onset in SOCS2-/- mice and was associated with reduced number of Th1 (CD3+CD4+IFN-γ+) cells in the spinal cord and brain. However, while in WT mice, maximal clinical EAE score was followed by a progressive recovery; the SOCS2-/- mice were unable to recover from locomotor impairment that occurred during the acute phase. There was a prolonged inflammatory response (increased Th1 and decreased Th2 and T regulatory cells) in the late phase of EAE in the CNS of SOCS2-/- mice. Transplantation of bone marrow cells from SOCS2-/- into irradiated WT mice resulted in higher lethality at the early phase of EAE. Altogether, these results suggest that SOCS2 plays a dual role in the immune response during EAE. It is necessary for damage during the acute phase damage but plays a beneficial role in the recovery stage of the disease.

scholarly journals Immunization Enhances Inflammation and Tissue Destruction in Response to Porphyromonas gingivalis

2006 ◽  
Vol 74 (4) ◽  
pp. 2286-2292 ◽  
Author(s):  
Cataldo W. Leone ◽  
Haneen Bokhadhoor ◽  
David Kuo ◽  
Tesfahun Desta ◽  
Julia Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Connective Tissue ◽  
Porphyromonas Gingivalis ◽  
Innate Immune Response ◽  
Periodontal Diseases ◽  
Critical Role ◽  
Innate Immune ◽  
Host Bacterium ◽  
Mrna Levels ◽  
Tissue Destruction

ABSTRACT It is well established that host-bacterium interactions play a critical role in the initiation and progression of periodontal diseases. By the use of inhibitors, it has been shown that mediators associated with the innate immune response significantly contribute to the disease process. Less is known regarding the role of the acquired immune response. To investigate mechanisms by which the acquired immune response to Porphyromonas gingivalis could affect connective tissue, we used a well-documented calvarial model to study host-bacterium interactions. Injection of P. gingivalis stimulated gamma interferon, interleukin 6, macrophage inflammatory protein 2, and monocyte chemoattractant protein 1 expression as determined by real-time PCR. Prior immunization against P. gingivalis significantly enhanced the mRNA levels of these cytokines and chemokines. Similarly, immunization significantly increased and prolonged the formation of a polymorphonuclear leukocyte and mononuclear cell infiltrate (P < 0.05). In addition, the area of connective tissue destruction, osteoclastogenesis, bone loss, mRNA expression of proapoptotic genes, and degree of fibroblast apoptosis were increased in immunized mice (P < 0.05). These results indicate that activation of the acquired immunity by P. gingivalis increases the inflammatory and destructive responses which occur in part through up-regulating the innate immune response and enhancing osteoclastogenesis and fibroblast apoptosis.

Abstract 16371: Targeted Delivery of Pulmonary Arterial Endothelial Cells Overexpressing Interleukin-8 Receptors Attenuates Liposaccharide-induced Lung Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Dongqi Xing ◽  
Samantha S Giordano ◽  
Amit Gaggar ◽  
Wenguang Feng ◽  
Yiu-Fai Chen ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Adhesion Molecule ◽  
Targeted Delivery ◽  
Inflammatory Cytokine ◽  
Critical Role ◽  
Neutrophil Infiltration ◽  
Interleukin 8 ◽  
Mrna Levels ◽  
Pulmonary Arterial

Background: Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, there is still no effective therapy for ALI/ARDS, and treatment options are largely limited to supportive care. Neutrophil-mediated inflammation and endothelial cell (EC) injury are unifying features of the pathogenesis of ALI/ARDS. Interleukin-8 (IL8) receptors IL8RA and IL8RB (ILRA/B) on neutrophil membranes bind to IL8 with high affinity and play a critical role in neutrophil recruitment to sites of injury and/or inflammation. This study tested the hypothesis that administration of rat pulmonary arterial ECs overexpressing IL8RA/B inhibits liposaccharide (LPS)-induced acute lung injury. Methods and Results: 12-wk-old ovariectomized SD rats were divided into three groups and received intra-peritoneal (i.p.) injection of saline (Sham); LPS (Escherichia coli 026:B6, Sigma-Aldrich, 10 mg/kg, i.p.) followed by i.v. infusion of saline; or LPS followed by i.v. transfusion of ECs overexpressing IL8RA/B (IL8RA/B-EC, 2hrs post LPS), respectively. 6 hrs after LPS treatment, pro-inflammatory cytokine/chemokine mRNA levels were measured by real-time, RT-PCR in homogenates of right lung. Neutrophil infiltration and lung injury were assessed by immunohistochemical staining and H&E staining in tissue sections of formalin-fixed, paraffin-embedded left lung. Expression of mRNA for adhesion molecule (P-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1), chemoattractant (cytokine-induced neutrophil chemoattractant-2 beta and monocyte chemoattractant protein-1), and pro-inflammatory cytokine (interleukin-6 and tumor necrosis factor-alpha) was markedly increased in lungs of LPS rats. Transfusion of IL8RA/B-ECs significantly attenuated expression of the pro-inflammatory mediators (by 50% to 70%) in LPS-injured lungs. Transfusion of IL8RA/B-ECs also significantly attenuated LPS-induced neutrophil infiltration and lung injury response. Conclusion: These provocative findings indicate that targeted delivery of ECs overexpressing IL8RA/B protects against LPS-induced acute lung injury.

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lidan Liu ◽  
Chaim Z. Aron ◽  
Cullen M. Grable ◽  
Adrian Robles ◽  
Xiangli Liu ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
Inflammatory Cytokine ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Mrna Levels ◽  
Wild Type ◽  
Cytokine Mrna ◽  
Protein Levels ◽  
Cytokine Levels

AbstractLevels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A−/−) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A−/− mice compared to wild type mice. Gavage of neonatal SP-A−/− mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A−/− mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.

scholarly journals Why Does SARS-CoV-2 Infection Induce Autoantibody Production?

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 380
Author(s):  
Ales Macela ◽  
Klara Kubelkova
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Host Cell ◽  
Critical Role ◽  
Cell Interaction ◽  
Immune Recognition ◽  
Autoantibody Production ◽  
Host Cell Interaction ◽  
Primary Virus

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient’s immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19.

scholarly journals Immune System Efficiency in Cancer and the Microbiota Influence

Pathobiology ◽  
2021 ◽  
pp. 1-17
Author(s):  
Ana Margarida Barbosa ◽  
Alexandra Gomes-Gonçalves ◽  
António G. Castro ◽  
Egídio Torrado
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Checkpoint Inhibitors ◽  
Therapeutic Response ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Antitumor Immune Response ◽  
System Efficiency ◽  
Novel Targets ◽  
Cancer Immunosurveillance

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.

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