scholarly journals Absence of cytotoxicity towards microglia of iron oxide (α-Fe2O3) nanorhombohedra

2016 ◽  
Vol 5 (3) ◽  
pp. 836-847 ◽  
Author(s):  
Crystal S. Lewis ◽  
Luisa Torres ◽  
Jeremy T. Miyauchi ◽  
Cyrus Rastegar ◽  
Jonathan M. Patete ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Cytotoxic Effects ◽  
Nanoparticle Exposure ◽  
Cellular Iron ◽  
Therapeutic Setting ◽  
The Central Nervous System ◽  
Factor Alpha

Abstract Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of N-Rhomb exposure in the presence of microglia, we have synthesized Rhodamine B (RhB)-labeled α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm. Internalization of RhB-labeled α-Fe2O3 N-Rhomb by microglia in the mouse brain was observed, and a dose-dependent increase in the cellular iron content as probed by cellular fluorescence was detected in cultured microglia after nanoparticle exposure. The cells maintained clear functional viability, exhibiting little to no cytotoxic effects after 24 and 48 hours at acceptable, physiological concentrations. Importantly, the nanoparticle exposure did not induce microglial cells to produce either tumor necrosis factor alpha (TNFα) or interleukin 1-beta (IL1β), two pro-inflammatory cytokines, nor did exposure stimulate the production of nitrites and reactive oxygen species (ROS), which are common indicators for the onset of inflammation. Finally, we propose that under the conditions of our experiments, i.e. in the presence of RhB labeled-α-Fe2O3 N-Rhomb maintaining concentrations of up to 100 μg mL−1 after 48 hours of incubation, the in vitro and in vivo internalization of RhB-labeled α-Fe2O3 N-Rhomb are likely to be clathrin-dependent, which represents a conventional mechanistic uptake route for most cells. Given the crucial role that microglia play in many neurological disorders, understanding the potential cytotoxic effects of these nanostructures is of fundamental importance if they are to be used in a therapeutic setting.

In vivo E-selectin upregulation correlates early with infiltration of PMN, later with PBL entry: MAbs block both

1996 ◽  
Vol 270 (1) ◽  
pp. H183-H193 ◽  
Author(s):  
R. M. Binns ◽  
S. T. Licence ◽  
A. A. Harrison ◽  
E. T. Keelan ◽  
M. K. Robinson ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Inflammatory Infiltration ◽  
Necrosis Factor Alpha ◽  
Inflammatory Processes ◽  
Factor Alpha ◽  
Kinetics Of ◽  
Necrosis Factor

The endothelial molecule E-selectin binds most leukocyte subsets in vitro. Yet its role in regulating the very different kinetics of inflammatory infiltration of different leukocyte subsets in vivo is unclear. The kinetics of E-selectin upregulation and polymorphonuclear leukocyte (PMN) and blood lymphocyte (PBL) localization in inflammation induced by interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), phytohemagglutinin (PHA), and phorbol myristate acetate (PMA) were investigated in a well-established inbred pig trafficking model. They differed markedly both for these three labeled indicators of inflammation and in each of the four inflammatory processes. In each, E-selectin upregulation correlated with early PMN entry and later with PBL infiltration but was more protracted than both. The importance of E-selectin was confirmed by marked inhibition of PMN and PBL entry (up to > 60%) by F(ab')2 anti-E-selectin. Involvement of other molecules was illustrated by similar or greater inhibition with anti-CD18 F(ab')2. We conclude that, like CD18, E-selectin is necessary for most PMN and PBL infiltration but alone is insufficient, consistent with the involvement of several alternative multistep molecular mechanisms in this entry.

scholarly journals Cytokine formation within rat glomeruli during experimental endotoxemia.

1993 ◽  
Vol 3 (11) ◽  
pp. 1783-1791
Author(s):  
B Fouqueray ◽  
C Philippe ◽  
A Herbelin ◽  
J Perez ◽  
R Ardaillou ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Lag Period ◽  
Bone Marrow Derived Cells ◽  
Factor Alpha ◽  
And Function ◽  
Lipopolysaccharide Challenge

Increasing evidence supports a role of cytokines, tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and IL-6 in the development of endotoxin-induced acute renal failure. Several activities of these cytokines require a local rather than a systemic production and function. Thus, this study investigates the chronology of cytokine expression in glomeruli isolated from normal rats or rats given iv lipopolysaccharide injections. Detectable levels of TNF alpha could be found in glomeruli isolated from normal rats as assessed by L-929 fibroblast lytic assay and ELISA. Glomeruli isolated from rats given lipopolysaccharide transiently released increased amounts of TNF alpha in relation to the dose of lipopolysaccharide (10 to 500 micrograms/kg body wt) and the lag period between lipopolysaccharide injection and glomerular isolation (20 to 120 min). TNF alpha was released in similar amounts by glomeruli from normal rats that were exposed in vitro to lipopolysaccharide challenge (0.01 to 10 micrograms/mL), indicating that lipopolysaccharide had direct effects on the release of TNF alpha from glomerular cells. These cells consisted mainly of resident cells because reduction of glomerular infiltration by bone marrow-derived cells after the irradiation of normal rats did not affect TNF alpha release. Glomerular IL-1 and IL-6 production was evaluated by specific bioassays under identical conditions. No IL-1 activity could be detected in the medium or within the glomerular cells at any time within 120 min after lipopolysaccharide injection. By contrast, glomerular IL-6 production was induced after lipopolysaccharide challenge both in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Human neutrophils produce high levels of the interleukin 1 receptor antagonist in response to granulocyte/macrophage colony-stimulating factor and tumor necrosis factor alpha.

1992 ◽  
Vol 176 (2) ◽  
pp. 593-598 ◽  
Author(s):  
S R McColl ◽  
R Paquin ◽  
C Ménard ◽  
A D Beaulieu
Keyword(s):  
De Novo ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Human Neutrophils ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Factor Alpha ◽  
Macrophage Colony

Neutrophils, an abundant cell type at sites of inflammation, have the ability to produce a number of cytokines, including interleukin 1 (IL-1), IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha). In this study, we have examined the ability of human neutrophils to produce the IL-1 receptor antagonist (IL-1Ra), a 17-23-kD protein recently isolated and cloned from macrophages. Since IL-1Ra has been shown to inhibit both the in vitro and in vivo effects of IL-1, its production by large numbers of tissue-invading neutrophils might provide a mechanism by which the effects of IL-1 are regulated in inflammation. Using antibodies that are specific for IL-1Ra and a cDNA probe encoding for this protein, we were able to show that neutrophils constitutively produce IL-1Ra. However, after activation by GM-CSF and TNF-alpha, IL-1Ra was secreted into the extracellular milieu where it constituted the major de novo synthesized product of activated neutrophils. None of a large array of other potent neutrophil agonists were found to affect the production of IL-1Ra by neutrophils. Quantitative measurements by enzyme-linked immunosorbent assay revealed that intracellular IL-1Ra is in eightfold excess of the amount secreted in supernatants when studying nonactivated neutrophils. However, in GM-CSF- and TNF-alpha-activated cells, this difference was reduced to values between four- and fivefold, as virtually all of the de novo synthesized IL-1Ra was secreted. In activated cells, the intracellular content of IL-1Ra was found to be in the 2-2.5-ng/ml range per 10(6) neutrophils, whereas levels reached the 0.5-ng/ml range in supernatants. This would imply that IL-1Ra is produced in excess of IL-1 by a factor of at least 100, an observation that is in agreement with the reported amounts of IL-1Ra needed to inhibit the proinflammatory effects of IL-1. Neutrophils isolated from an inflammatory milieu, the synovial fluid of patients with rheumatoid arthritis, were found to respond to GM-CSF and TNF-alpha in terms of IL-1Ra synthesis, indicating that the in vitro observations made in this study are likely to occur in an inflammatory setting in vivo.

Granisetron ameliorates acetic acid-induced colitis in rats

2010 ◽  
Vol 29 (4) ◽  
pp. 321-328 ◽  
Author(s):  
Gohar Fakhfouri ◽  
Reza Rahimian ◽  
Ali Daneshmand ◽  
Arash Bahremand ◽  
Mohammad Reza Rasouli ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Interleukin 1 ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Concurrent Administration ◽  
Necrosis Factor Alpha ◽  
Inflammatory Bowel ◽  
Factor Alpha

Inflammatory bowel disease (IBD) is a chronically relapsing inflammation of the gastrointestinal tract, of which the definite etiology remains ambiguous. Considering the adverse effects and incomplete efficacy of currently administered drugs, it is indispensable to explore new candidates with more desirable therapeutic profiles. 5-HT 3 receptor antagonists have shown analgesic and anti-inflammatory properties in vitro and in vivo. This study aims to investigate granisetron, a 5-HT 3 receptor antagonist, in acetic acid-induced rat colitis and probable involvement of 5-HT3 receptors. Colitis was rendered by instillation of 1 mL of 4% acetic acid (vol/vol) and after 1 hour, granisetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5-HT 3 receptor agonist, or granisetron + mCPBG was given intraperitoneally. Twenty-four hours following colitis induction, animals were sacrificed and distal colons were assessed macroscopically, histologically and biochemically (malondialdehyde, myeloperoxidase, tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6). Granisetron or dexamethasone significantly (p < .05) improved macroscopic and histologic scores, curtailed myeloperoxidase activity and diminished colonic levels of inflammatory cytokines and malondialdehyde. The protective effects of granisetron were reversed by concurrent administration of mCPBG. Our data suggests that the salutary effects of granisetron in acetic acid colitis could be mediated by 5-HT3 receptors.

Erythropoietin gene expression is suppressed after lipopolysaccharide or interleukin-1 beta injections in rats

1997 ◽  
Vol 273 (3) ◽  
pp. R1067-R1071 ◽  
Author(s):  
S. Frede ◽  
J. Fandrey ◽  
H. Pagel ◽  
T. Hellwig ◽  
W. Jelkmann
Keyword(s):  
Gene Expression ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Hypoxia Exposure ◽  
Factor Alpha

Proinflammatory cytokines play an important role in the pathogenesis of anemia in inflammatory diseases. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been reported to inhibit the synthesis of erythropoietin (EPO) in vitro. To evaluate the in vivo significance of this observation, we have investigated effects of the administration of bacterial lipopolysaccharide (LPS) and IL-1 beta on renal EPO production in rats. Measurements by competitive reverse-transcription polymerase chain reaction showed that EPO mRNA levels were significantly reduced in the kidneys of normoxic rats 6 h after the injection of LPS (0.1 or 1 mg/kg). In addition, LPS and IL-1 beta (1 microgram/kg) inhibited the increase in EPO mRNA and plasma EPO levels when administered to rats before hypoxia exposure (8% O2 in the inspiratory gas). Evidence for an inflammatory reaction in the kidneys of LPS-treated rats was provided by measurements of greatly elevated renal TNF-alpha mRNA levels. Furthermore, kidneys isolated from LPS-created rats produced less immunoreactive EPO when perfused hypoxically in vitro for 2 h. Thus mediators of the immune response inhibit renal EPO gene expression in vivo, which is relevant with respect to the impaired synthesis of EPO in inflammatory diseases in humans.

scholarly journals Sialyl Lewisx (sLex) and an sLexMimetic, CGP69669A, Disrupt E-Selectin–Dependent Leukocyte Rolling In Vivo

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 475-483 ◽  
Author(s):  
Keith E. Norman ◽  
Gary P. Anderson ◽  
Hartmut C. Kolb ◽  
Klaus Ley ◽  
Beat Ernst
Keyword(s):  
Leukocyte Rolling ◽  
Sialyl Lewisx ◽  
Necrosis Factor Alpha ◽  
Rolling Velocity ◽  
Beneficial Effects ◽  
Selectin Family ◽  
Factor Alpha ◽  
Observable Event

Abstract Leukocyte rolling is the earliest observable event in their recruitment from the circulation to inflamed tissue. This rolling is mediated largely by interaction between the selectin family of adhesion molecules and their glycosylated ligands. Although the nature of these ligands and their interaction with the selectins is not fully understood, it is accepted that expression of fucosylated sialylated glycans such as sialyl Lewisx (sLex) is required for function. Despite findings that sLex inhibits binding of leukocytes to E-selectin in vitro, and has beneficial effects in inflammatory disease models, inhibition of E-selectin–dependent leukocyte rolling in vivo has not been described. Functional overlap between the selectins has been noted and reduction of rolling by E-selectin antibodies only occurs if P-selectin is absent or blocked. We demonstrate that leukocyte rolling velocity in tumor necrosis factor alpha (TNFα)-stimulated mouse cremaster is increased following treatment with either sLex or the sLex-mimetic CGP69669A and that rolling is dramatically reduced if CGP69669A is applied in the presence of anti–P-selectin antibody. These effects are characteristic of E-selectin antagonism. In contrast, surgically stimulated (L- or P-selectin–dependent) rolling is unaffected by either sLex or CGP69669A. Our data demonstrate that CGP69669A is an effective and selective antagonist of E-selectin in vivo.

P-selectin glycoprotein ligand-1 supports rolling on E- and P-selectin in vivo

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3585-3591 ◽  
Author(s):  
Keith E. Norman ◽  
Andreas G. Katopodis ◽  
Gebhard Thoma ◽  
Frank Kolbinger ◽  
Anne E. Hicks ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Rolling Velocity ◽  
Selectin Ligand ◽  
Factor Alpha ◽  
Observable Event ◽  
Slow Rolling ◽  
Necrosis Factor

Abstract Selectin-dependent rolling is the earliest observable event in the recruitment of leukocytes to inflamed tissues. Several glycoproteins decorated with sialic acid, fucose, and/or sulfate have been shown to bind the selectins. The best-characterized selectin ligand is P-selectin glycoprotein-1 (PSGL-1) that supports P-selectin– dependent rolling in vitro and in vivo. In vitro studies have suggested that PSGL-1 may also be a ligand for E- and L-selectins. To study the in vivo function of PSGL-1, without the influence of other leukocyte proteins, the authors observed the interaction of PSGL-1–coated microspheres in mouse venules stimulated to express P- and/or E-selectin. Microspheres coated with functional recombinant PSGL-1 rolled in surgically stimulated and tumor necrosis factor alpha (TNFα)-stimulated mouse venules. P-selectin deficiency or inhibition abolished microsphere rolling in surgically and TNFα-stimulated venules, whereas E-selectin deficiency or inhibition increased microsphere rolling velocity in TNFα-stimulated venules. The results suggest that P-selectin–PSGL-1 interaction alone is sufficient to mediate rolling in vivo and that E-selectin–PSGL-1 interaction supports slow rolling.

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