scholarly journals Effects of Immunomodulatory Substances on Phagocytosis of A by Human Microglia

2010 ◽  
Vol 2010 ◽  
pp. 1-18 ◽  
Author(s):  
Erik Hjorth ◽  
Dan Frenkel ◽  
Howard Weiner ◽  
Marianne Schultzberg
Keyword(s):  
Nitric Oxide ◽  
Membrane Protein ◽  
Inducible Nitric Oxide Synthase ◽  
Inflammatory Markers ◽  
Interleukin 1 ◽  
Type I ◽  
Human Microglia ◽  
Amyloid A ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Glial activation and increased inflammation characterize neuropathology in Alzheimer's disease (AD). The aim was to develop a model for studying phagocytosis of -amyloid (A) peptide by human microglia and to test effects thereupon by immunomodulatory substances. Human CHME3 microglia showed intracellular A colocalized with lysosome-associated membrane protein-2, indicating phagocytosis. This was increased by interferon-, and to a lesser degree with Protollin, a proteosome-based adjuvant. Secretion of brain-derived neurotrophic factor (BDNF) was decreased by A and by interferon- and interleukin-1. These cytokines, but not A, stimulated interleukin-6 release. Microglia which phagocytosed A exhibited a higher degree of expression of interleukin-1 receptor type I and inducible nitric oxide synthase. In conclusion, we show that human microglia are able to phagocytose A and that this is associated with expression of inflammatory markers. A and interferon- decreased BDNF secretion suggesting a new neuropathological role for A and the inflammation accompanying AD.

scholarly journals Inducible Nitric Oxide Synthase Is Not Essential for Control of Trypanosoma cruzi Infection in Mice

2004 ◽  
Vol 72 (7) ◽  
pp. 4081-4089 ◽  
Author(s):  
Kara L. Cummings ◽  
Rick L. Tarleton
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Trypanosoma Cruzi ◽  
Inducible Nitric Oxide Synthase ◽  
Interleukin 1 ◽  
Mouse Strains ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Immune control of many intracellular pathogens, including Trypanosoma cruzi, is reported to be dependent on the production of nitric oxide. In this study, we show that mice deficient in inducible nitric oxide synthase (iNOS or NOS2) exhibit resistance to T. cruzi infection that is comparable to that of wild-type mice. This is the case for two iNOS-deficient mouse strains, Nos2tm1Lau and Nos2 N5, infected with the Brazil or Tulahuen strain of T. cruzi. In all cases, blood parasitemia, tissue parasite load, and survival rates are similar between wild-type and iNOS-deficient mice. In contrast, both wild-type and Nos2tm1Lau mice died within 32 days postinfection when treated with the nitric oxide synthase inhibitor aminoguanidine. Increased transcription of NOS1 or NOS3 is not found in iNOS-knockout (KO) mice, indicating that the absence of nitric oxide production through iNOS is not compensated for by increased production of other NOS isoforms. However, Nos2tm1Lau mice exhibit enhanced expression of tumor necrosis factor alpha, interleukin-1, and macrophage inflammatory protein 1α compared to that of wild-type mice, and these alterations may in part compensate for the lack of iNOS. These results clearly show that iNOS is not required for control of T. cruzi infection in mice.

In Situ Detection of Inflammatory Cytokines and Apoptosis in Pemphigus Foliaceus Patients

2009 ◽  
Vol 133 (1) ◽  
pp. 97-100
Author(s):  
Denise Bertulucci Rocha Rodrigues ◽  
Sanivia Aparecida Lima Pereira ◽  
Marlene Antônia dos Reis ◽  
Sheila Jorge Adad ◽  
João Eduardo Caixeta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Proinflammatory Cytokines ◽  
Interleukin 1 ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Pemphigus Foliaceus ◽  
Endemic Pemphigus Foliaceus ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Abstract Context.—Endemic pemphigus foliaceus, or fogo selvagem, is a chronic autoimmune disease characterized by the formation of intraepidermal blisters that reduce adhesion between keratinocytes. Endemic pemphigus foliaceus is associated with the presence of autoantibodies and high levels of cytokines involved in the inflammatory response. Objectives.—To evaluate the expression of the proinflammatory cytokines interleukin 1, interferon γ, and tumor necrosis factor α; the proapoptotic inducers Fas and inducible nitric oxide synthase; and the apoptosis inhibitor Bcl-2; and to evaluate the presence of apoptosis. Design.—Skin biopsies from 13 patients with endemic pemphigus foliaceus and controls were evaluated by immunohistochemistry and apoptosis was determined by terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling assay. Results.—Proinflammatory cytokines were only detected in cells of the inflammatory exudate. Inducible nitric oxide synthase, Fas, and Bcl-2 were expressed by both epithelial and inflammatory cells. Epithelial apoptosis was observed in 12 cases (92.3%), and subepithelial apoptosis in 11 cases (85%). Conclusions.—This study suggests that apoptosis as well as the local production of proinflammatory cytokines are associated with endemic pemphigus foliaceus lesions. These results may contribute to the development of new therapeutic approaches to endemic pemphigus foliaceus.

scholarly journals Glutathione inhibits expression of the proinflammatory biomarker inducible nitric oxide synthase in hepatocytes

2018 ◽  
Vol 8 (12) ◽  
pp. 544
Author(s):  
Richi Nakatake ◽  
Masaya Kotsuka ◽  
Yuki Hashimoto ◽  
Masahiko Hatta ◽  
Morihiko Ishizaki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Liver Injury ◽  
Inducible Nitric Oxide Synthase ◽  
Type I ◽  
Tnf Α ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Inducible Nitric Oxide ◽  
Inos Induction

Background: Intracellular glutathione (GSH) plays an important regulatory role in the host response to liver injury. However, there have been few scientific reports on the anti-inflammatory effects of GSH. In the inflamed liver, proinflammatory cytokines stimulate liver cells, followed by expression of inducible nitric oxide synthase (iNOS). Excessive nitric oxide (NO) levels produced by iNOS are one of the factors involved in liver injury. Therefore, inhibiting iNOS induction is important for preventing liver injury. This study aimed to investigate the protective effects of GSH on the liver by examining interleukin (IL)-1β-stimulated hepatocytes.Methods: Primary cultured rat hepatocytes were treated with IL-1β in the presence or absence of GSH. Induction of iNOS and its signaling pathway were analyzed.Results: Addition of GSH decreased IL-1β-induced iNOS protein and mRNA expression levels, which resulted in inhibition of NO production. GSH also decreased tumor necrosis factor (TNF)-α and IL-6 mRNA expression. GSH blocked “type I IL-1 receptor upregulation”, one of the essential signaling pathways for iNOS induction, through inactivation of an upstream kinase, phosphatidylinositol 3-kinase/Akt. In contrast, GSH had no effects on degradation of IκB and activation of NF-ĸB (nuclear translocation and its DNA binding). Transfection experiments revealed that GSH reduced iNOS mRNA levels at the promoter transactivation and mRNA stabilization steps. Delayed administration of GSH after IL-1β addition also inhibited iNOS induction. Conclusions: Our study suggests that GSH affects induction of inflammatory mediators, including iNOS and TNF-α, indicating its therapeutic potential for organ injuries, especially for the liver.Keywords: glutathione, inducible nitric oxide synthase, liver injury, primary cultured hepatocytes, type I interleukin-1 receptor, tumor necrosis factor-α

Sign in / Sign up

Export Citation Format

Share Document