Metallothionein Treatment Reduces Proinflammatory Cytokines IL-6 and TNF-α and Apoptotic Cell Death during Experimental Autoimmune Encephalomyelitis (EAE)

2001 ◽  
Vol 170 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Milena Penkowa ◽  
Juan Hidalgo
Keyword(s):  
Cell Death ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Proinflammatory Cytokines ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Autoimmune Encephalomyelitis ◽  
Tnf Α ◽  
Experimental Autoimmune

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

2021 ◽  
Author(s):  
William E. Barclay ◽  
M. Elizabeth Deerhake ◽  
Makoto Inoue ◽  
Toshiaki Nonaka ◽  
Kengo Nozaki ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Animal Model ◽  
Cell Death ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammasome Activation ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.

Contribution of TNF-α to Leukocyte Adhesion, Vascular Leakage, and Apoptotic Cell Death in Endotoxin-Induced Uveitis In Vivo

2003 ◽  
Vol 44 (5) ◽  
pp. 2184 ◽  
Author(s):  
Kan Koizumi ◽  
Vassiliki Poulaki ◽  
Sven Doehmen ◽  
Gerhard Welsandt ◽  
Sven Radetzky ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Leukocyte Adhesion ◽  
Apoptotic Cell Death ◽  
Vascular Leakage ◽  
Tnf Α

Reciprocal stimulation between TNF-α and nitric oxide may exacerbate CNS inflammation in experimental autoimmune encephalomyelitis

1998 ◽  
Vol 89 (1-2) ◽  
pp. 122-130 ◽  
Author(s):  
Deming Sun ◽  
Christopher Coleclough ◽  
Ligong Cao ◽  
Xianzhen Hu ◽  
Sheher Sun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Tnf Α ◽  
Experimental Autoimmune

scholarly journals Shiga Toxins Activate the NLRP3 Inflammasome Pathway To Promote Both Production of the Proinflammatory Cytokine Interleukin-1β and Apoptotic Cell Death

2015 ◽  
Vol 84 (1) ◽  
pp. 172-186 ◽  
Author(s):  
Moo-Seung Lee ◽  
Haenaem Kwon ◽  
Eun-Young Lee ◽  
Dong-Jae Kim ◽  
Jong-Hwan Park ◽  
...  
Keyword(s):  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Interleukin 1Β ◽  
Dependent Manner ◽  
Shiga Toxins ◽  
Caspase 1 ◽  
Immune Signaling Pathway ◽  
Tnf Α

Shiga toxin (Stx)-mediated immune responses, including the production of the proinflammatory cytokines tumor necrosis-α (TNF-α) and interleukin-1β (IL-1β), may exacerbate vascular damage and accelerate lethality. However, the immune signaling pathway activated in response to Stx is not well understood. Here, we demonstrate that enzymatically active Stx, which leads to ribotoxic stress, triggers NLRP3 inflammasome-dependent caspase-1 activation and IL-1β secretion in differentiated macrophage-like THP-1 (D-THP-1) cells. The treatment of cells with a chemical inhibitor of glycosphingolipid biosynthesis, which suppresses the expression of the Stx receptor globotriaosylceramide and subsequent endocytosis of the toxin, substantially blocked activation of the NLRP3 inflammasome and processing of caspase-1 and IL-1β. Processing and release of both caspase-1 and IL-1β were significantly reduced or abolished in Stx-intoxicated D-THP-1 cells in which the expression of NLRP3 or ASC was stably knocked down. Furthermore, Stx mediated the activation of caspases involved in apoptosis in an NLRP3- or ASC-dependent manner. In Stx-intoxicated cells, the NLRP3 inflammasome triggered the activation of caspase-8/3, leading to the initiation of apoptosis, in addition to caspase-1-dependent pyroptotic cell death. Taken together, these results suggest that Stxs trigger the NLRP3 inflammasome pathway to release proinflammatory IL-1β as well as to promote apoptotic cell death.

scholarly journals Intravenous Liposomal Prednisolone Downregulates In Situ TNF-α Production by T-cells in Experimental Autoimmune Encephalomyelitis

2003 ◽  
Vol 51 (9) ◽  
pp. 1241-1244 ◽  
Author(s):  
Jens Schmidt ◽  
Josbert M. Metselaar ◽  
Ralf Gold
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
High Dose ◽  
Autoimmune Encephalomyelitis ◽  
Double Labeling ◽  
Formalin Fixed Paraffin ◽  
Tnf Α ◽  
Formalin Fixed Paraffin Embedded ◽  
Factor Α ◽  
Experimental Autoimmune

Multiple sclerosis (MS) relapses are treated with high-dose IV glucocorticosteroids. Here we investigated mechanisms of long-circulating polyethylene glycol-coated liposomes encapsulating prednisolone (PL) in adoptive transfer experimental autoimmune encephalomyelitis. Rats received IV 10 mg/kg PL 6, 18, or 42 hr before sacrifice at disease maximum. In formalin-fixed, paraffin-embedded spinal cord we employed a nonfluorescent immunohistochemical (IHC) double labeling. We stained for tumor necrosis factor-α (TNF-α) in combination with a T-cell antigen. Compared with PBS-containing liposomes, PL at 18 hr, and more at 42 hr, significantly reduced the rate of TNF-α double-labeled T-cells. This correlated with an ameliorated disease score at day 5 after PL 42 hr. Our results help to further understand mechanisms of action of drug targeting by liposomal steroids, with possible implications for treatment of autoimmune disorders such as MS.

Cannabinoid CB1 receptors regulate neuronal TNF-α effects in experimental autoimmune encephalomyelitis

2011 ◽  
Vol 25 (6) ◽  
pp. 1242-1248 ◽  
Author(s):  
Silvia Rossi ◽  
Roberto Furlan ◽  
Valentina De Chiara ◽  
Luca Muzio ◽  
Alessandra Musella ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Cb1 Receptors ◽  
Autoimmune Encephalomyelitis ◽  
Tnf Α ◽  
Experimental Autoimmune

Induction of apoptotic cell death by 2′-hydroxycinnamaldehyde is involved with ERK-dependent inactivation of NF-κB in TNF-α-treated SW620 colon cancer cells

2005 ◽  
Vol 70 (8) ◽  
pp. 1147-1157 ◽  
Author(s):  
Seung Ho Lee ◽  
Chung Woo Lee ◽  
Jae Woong Lee ◽  
Myoung Suk Choi ◽  
Dong Ju Son ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Colon Cancer Cells ◽  
Dependent Inactivation ◽  
Tnf Α

Apoptotic cell death of T-lymphocytes in experimental autoimmune neuritis of the Lewis rat

1994 ◽  
Vol 176 (1) ◽  
pp. 75-79 ◽  
Author(s):  
Uwe K. Zettl ◽  
Ralf Gold ◽  
Hans-Peter Hartung ◽  
Klaus V. Toyka
Keyword(s):  
Cell Death ◽  
T Lymphocytes ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Experimental Autoimmune Neuritis ◽  
Lewis Rat ◽  
Experimental Autoimmune

Effect of 10-day forced treadmill training on neurotrophic factors in experimental autoimmune encephalomyelitis

2013 ◽  
Vol 38 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Darpan I. Patel ◽  
Lesley J. White
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Disease Progression ◽  
Wheel Running ◽  
Treadmill Running ◽  
Clinical Effects ◽  
Control Groups ◽  
Autoimmune Encephalomyelitis ◽  
Tnf Α ◽  
The Impact ◽  
Experimental Autoimmune

The impact of exercise on disease progression in multiple sclerosis (MS) is unclear. In the present study, we evaluated the clinical effects of forced wheel running on rats induced with experimental autoimmune encephalomyelitis (EAE), a model of MS. Female Lewis rats (n = 40) were randomly assigned to 1 of 4 groups prior to inoculation: EAE exercise (EAE-Ex), EAE sedentary (EAE-Sed), control exercise (Con-Ex), or control sedentary (Con-Sed). Exercise training was composed of forced treadmill running at increasing intensity across 10 consecutive days. No significant differences in clinical disability were observed in the EAE groups at the conclusion of this study. Furthermore, no significant differences in brain mass were observed across groups. Analysis of brain tissue proteins revealed that tumour necrosis factor-α (TNF-α) concentrations were higher in both EAE groups compared with the control groups (p < 0.05); however, no significant differences were seen between the EAE-Ex and EAE-Sed groups. The Con-Ex group had lower whole-brain TNF-α compared with the Con-Sed group (p < 0.05). Nerve growth factor concentrations were greater in the EAE-Ex animals compared with both control groups (p < 0.05 for both). No differences were seen in brain-derived neurotrophic factor. Our results indicate that aerobic exercise can modulate the proteins associated with disability in EAE; however, further research is required to understand the total impact of exercise on EAE disability and disease progression.

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