scholarly journals Sustained Surface ICAM-1 Expression and Transient PDGF-B Production by Phorbol Myristate Acetate-Activated THP-1 Cells Harboring Blau Syndrome-Associated NOD2 Mutations

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 335
Author(s):  
Mizuho Nishiyama ◽  
Hong-jin Li ◽  
Ikuo Okafuji ◽  
Akihiko Fujisawa ◽  
Mizue Ehara ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Phorbol Myristate Acetate ◽  
Giant Cells ◽  
Granuloma Formation ◽  
Blau Syndrome ◽  
Myristate Acetate ◽  
Altered Expression ◽  
Nucleotide Oligomerization

Objectives: Blau syndrome is a distinct class of autoinflammatory syndrome presenting with early-onset systemic granulomatosis. Blau syndrome-causing NOD2 mutations located in the central nucleotide-oligomerization domain induce ligand-independent basal NF-κB activation in an in vitro reporter assay. However, the precise role of this signaling on granuloma formation has not yet been clarified. Methods: Blau syndrome-causing NOD2 mutations were introduced into human monocytic THP-1 cells, and their morphological and molecular changes from parental cells were analyzed. Identified molecules with altered expression were examined in the patient’s lesional skin by immunostaining. Results: Although the production of proinflammatory cytokines was not altered without stimulation, mutant NOD2-expressing THP-1 cells attached persistently to the culture plate after stimulation with phorbol myristate acetate. Sustained surface ICAM-1 expression was observed in association with this phenomenon, but neither persistent ICAM-1 mRNA expression nor impaired ADAM17 mRNA expression was revealed. However, the transient induction of PDGF-B mRNA expression was specifically observed in stimulated THP-1 derivatives. In the granulomatous skin lesion of a Blau syndrome patient, ICAM-1 and PDGF-B were positively immunostained in NOD2-expressing giant cells. Conclusions: Sustained surface ICAM-1 expression and transient PDGF-B production by newly differentiating macrophages harboring mutant NOD2 might play a role in granuloma formation in Blau syndrome.

Role of hypochlorous acid inTrypanosoma musculikilling by phagocytes

Parasitology ◽  
1989 ◽  
Vol 98 (2) ◽  
pp. 253-257 ◽  
Author(s):  
P. Vincendeau ◽  
S. Daulouède ◽  
B. Veyret
Keyword(s):  
Phorbol Myristate Acetate ◽  
Hypochlorous Acid ◽  
Peritoneal Macrophages ◽  
Mononuclear Phagocytes ◽  
Myristate Acetate ◽  
Trypanocidal Activity

SUMMARYTrypanosoma musculiare readily killed when phagocytosed by mononuclear phagocytes but the nature of the mediators of this cytotoxicity is unclear. Among the most potent mediators are oxygen-derived species. The generation of chemilumine-scence (CL) by peritoneal macrophages from 12 dayT. musculi-infected mice, which phagocytose and kill parasites when opsonizing antibodies are present, was recorded in the presence of antibody-coated trypanosomes. Taurine, a specific quencher of hypochlorous acid (HOCl) inhibited CL production by peritoneal macrophages, showing that HOCl is produced during phagocytosis ofT. musculi.In vitro, HOCl alone exerted a powerful trypanocidal activity which was inhibited in the presence of specific quenchers. The role of HOCl generated by phagocytes in trypanosome killing was studied using granulocytes which produce more oxygen-derived species than macrophages when stimulated. Phorbol myristate acetate-triggered granulocytes can destroyT. musculiand trypanosome killing is inhibited in the presence of taurine. These data demonstrate that HOC1 produced by phagocytes can effectively destroyT. musculi.

scholarly journals Identification of a microRNA signature in renal fibrosis: role of miR-21

2011 ◽  
Vol 301 (4) ◽  
pp. F793-F801 ◽  
Author(s):  
Abolfazl Zarjou ◽  
Shanzhong Yang ◽  
Edward Abraham ◽  
Anupam Agarwal ◽  
Gang Liu
Keyword(s):  
Epithelial Cells ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Response To Treatment ◽  
Tubular Epithelial Cells ◽  
Altered Expression ◽  
Tnf Α ◽  
Tgf Β1

Renal fibrosis is a final stage of many forms of kidney disease and leads to impairment of kidney function. The molecular pathogenesis of renal fibrosis is currently not well-understood. microRNAs (miRNAs) are important players in initiation and progression of many pathologic processes including diabetes, cancer, and cardiovascular disease. However, the role of miRNAs in kidney injury and repair is not well-characterized. In the present study, we found a unique miRNA signature associated with unilateral ureteral obstruction (UUO)-induced renal fibrosis. We found altered expression in UUO kidneys of miRNAs that have been shown to be responsive to stimulation by transforming growth factor (TGF)-β1 or TNF-α. Among these miRNAs, miR-21 demonstrated the greatest increase in UUO kidneys. The enhanced expression of miR-21 was located mainly in distal tubular epithelial cells. miR-21 expression was upregulated in response to treatment with TGF-β1 or TNF-α in human renal tubular epithelial cells in vitro. Furthermore, we found that blocking miR-21 in vivo attenuated UUO-induced renal fibrosis, presumably through diminishing the expression of profibrotic proteins and reducing infiltration of inflammatory macrophages in UUO kidneys. Our data suggest that targeting specific miRNAs could be a novel therapeutic approach to treat renal fibrosis.

scholarly journals Characterisation of Osteopontin in an In Vitro Model of Embryo Implantation

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 432 ◽  
Author(s):  
Stéphane C Berneau ◽  
Peter T Ruane ◽  
Daniel R Brison ◽  
Susan J Kimber ◽  
Melissa Westwood ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Embryo Implantation ◽  
Giant Cells ◽  
Ishikawa Cell ◽  
Altered Expression ◽  
Ishikawa Cells ◽  
Cell Layers ◽  
Endometrial Epithelium ◽  
Vitro Model

At the onset of pregnancy, embryo implantation is initiated by interactions between the endometrial epithelium and the outer trophectoderm cells of the blastocyst. Osteopontin (OPN) is expressed in the endometrium and is implicated in attachment and signalling roles at the embryo–epithelium interface. We have characterised OPN in the human endometrial epithelial Ishikawa cell line using three different monoclonal antibodies, revealing at least nine distinct molecular weight forms and a novel secretory pathway localisation in the apical domain induced by cell organisation into a confluent epithelial layer. Mouse blastocysts co-cultured with Ishikawa cell layers served to model embryo apposition, attachment and initial invasion at implantation. Exogenous OPN attenuated initial, weak embryo attachment to Ishikawa cells but did not affect the attainment of stable attachment. Notably, exogenous OPN inhibited embryonic invasion of the underlying cell layer, and this corresponded with altered expression of transcription factors associated with differentiation from trophectoderm (Gata2) to invasive trophoblast giant cells (Hand1). These data demonstrate the complexity of endometrial OPN forms and suggest that OPN regulates embryonic invasion at implantation by signalling to the trophectoderm.

Multinucleated rat alveolar macrophages express functional receptors for calcitonin

1991 ◽  
Vol 261 (6) ◽  
pp. F1026-F1032 ◽  
Author(s):  
A. Vignery ◽  
M. J. Raymond ◽  
H. Y. Qian ◽  
F. Wang ◽  
S. A. Rosenzweig
Keyword(s):  
Plasma Membrane ◽  
Alveolar Macrophages ◽  
Giant Cells ◽  
Mononuclear Phagocytes ◽  
Inflammatory Reactions ◽  
Calcitonin Gene ◽  
Novel Model

The fusion of mononuclear phagocytes occurs spontaneously in vivo and leads to the differentiation of either multinucleated giant cells or osteoclasts in chronic inflammatory sites or in bone, respectively. Although osteoclasts are responsible for resorbing bone, the functional role of giant cells in chronic inflammatory reactions and tumors remains poorly understood. We recently reported that the plasma membrane of multinucleated macrophages is, like that of osteoclasts, enriched in Na-K-adenosinetriphosphatases (ATPases). We also observed that the localization of their Na-K-ATPases is restricted to the nonadherent domain of the plasma membrane of cells both in vivo and in vitro, thus imposing a functional polarity on their organization. By following this observation, we wished to investigate whether these cells also expressed, like osteoclasts, functional receptors for calcitonin (CT). To this end, alveolar macrophages were fused in vitro, and both their structural and functional association with CT was analyzed and compared with those of mononucleated peritoneal and alveolar macrophages. Evidence is presented that multinucleated alveolar macrophages express a high copy number of functional receptors for CT. Our results also indicate that alveolar macrophages, much like peritoneal, express functional receptors for calcitonin gene-related peptide. It is suggested that multinucleated rat alveolar macrophages offer a novel model system to study CT receptors and that calcitonin may control local immune reactions where giant cells differentiate.

“Autoregulation” of Human Neutrophil Activation In Vitro: Regulation of Phorbol Myristate Acetate-Induced Neutrophil Activation by Cell Density

1990 ◽  
Vol 47 (5) ◽  
pp. 457-474 ◽  
Author(s):  
Stephen P. Peters ◽  
Franklin Cerasoli ◽  
Kurt H. Albertine ◽  
Marlys H. Gee ◽  
David Berd ◽  
...  
Keyword(s):  
Cell Density ◽  
Phorbol Myristate Acetate ◽  
Human Neutrophil ◽  
Neutrophil Activation ◽  
Myristate Acetate

scholarly journals Mid-Gestation lethality of Atxn2l-Ablated Mice

2020 ◽  
Vol 21 (14) ◽  
pp. 5124 ◽  
Author(s):  
Jana Key ◽  
Patrick N. Harter ◽  
Nesli-Ece Sen ◽  
Elise Gradhand ◽  
Georg Auburger ◽  
...  
Keyword(s):  
Giant Cells ◽  
Neural Cells ◽  
Rna Surveillance ◽  
Extended Lifespan ◽  
Ataxin 2 ◽  
Locomotor Deficits ◽  
Lateral Sclerosis

Depletion of yeast/fly Ataxin-2 rescues TDP-43 overexpression toxicity. In mouse models of Amyotrophic Lateral Sclerosis via TDP-43 overexpression, depletion of its ortholog ATXN2 mitigated motor neuron degeneration and extended lifespan from 25 days to >300 days. There is another ortholog in mammals, named ATXN2L (Ataxin-2-like), which is almost uncharacterized but also functions in RNA surveillance at stress granules. We generated mice with Crispr/Cas9-mediated deletion of Atxn2l exons 5-8, studying homozygotes prenatally and heterozygotes during aging. Our novel findings indicate that ATXN2L absence triggers mid-gestational embryonic lethality, affecting female animals more strongly. Weight and development stages of homozygous mutants were reduced. Placenta phenotypes were not apparent, but brain histology showed lamination defects and apoptosis. Aged heterozygotes showed no locomotor deficits or weight loss over 12 months. Null mutants in vivo displayed compensatory efforts to maximize Atxn2l expression, which were prevented upon nutrient abundance in vitro. Mouse embryonal fibroblast cells revealed more multinucleated giant cells upon ATXN2L deficiency. In addition, in human neural cells, transcript levels of ATXN2L were induced upon starvation and glucose and amino acids exposure, but this induction was partially prevented by serum or low cholesterol administration. Neither ATXN2L depletion triggered dysregulation of ATXN2, nor a converse effect was observed. Overall, this essential role of ATXN2L for embryogenesis raises questions about its role in neurodegenerative diseases and neuroprotective therapies.

scholarly journals The Alternative Faces of Macrophage Generate Osteoclasts

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
N. Lampiasi ◽  
R. Russo ◽  
F. Zito
Keyword(s):  
Macrophage Polarization ◽  
Giant Cells ◽  
Gm Csf ◽  
Receptor Activator ◽  
Inflammatory Stimuli ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Alternatively Activated

The understanding of how osteoclasts are generated and whether they can be altered by inflammatory stimuli is a topic of particular interest for osteoclastogenesis. It is known that the monocyte/macrophage lineage gives rise to osteoclasts (OCs) by the action of macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL), which induce cell differentiation through their receptors, c-fms and RANK, respectively. The multinucleated giant cells (MGCs) generated by the engagement of RANK/RANKL are typical OCs. Nevertheless, very few studies have addressed the question of which subset of macrophages generates OCs. Indeed, two main subsets of macrophages are postulated, the inflammatory or classically activated type (M1) and the anti-inflammatory or alternatively activated type (M2). It has been proposed that macrophages can be polarizedin vitrotowards a predominantly M1 or M2 phenotype with the addition of granulocyte macrophage- (GM-) CSF or M-CSF, respectively. Various inflammatory stimuli known to induce macrophage polarization, such as LPS or TNF-α, can alter the type of MGC obtained from RANKL-induced differentiation. This review aims to highlight the role of immune-related stimuli and factors in inducing macrophages towards the osteoclastogenesis choice.

Dobutamine Inhibits Phorbol-Myristate-Acetate-Induced Activation of Nuclear Factor-??B in Human T Lymphocytes In Vitro

2004 ◽  
pp. 1508-1515 ◽  
Author(s):  
Torsten Loop ◽  
Tobias Bross ◽  
Matjaz Humar ◽  
Alexander Hoetzel ◽  
Rene Schmidt ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Phorbol Myristate Acetate ◽  
Nuclear Factor ◽  
Myristate Acetate ◽  
Factor B ◽  
Human T Lymphocytes
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