A morphological and ultrastructural investigation of normal mouse brain tissue after intracerebral injection of tumor necrosis factor

1992 ◽  
Vol 77 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Toshiki Yamasaki ◽  
Haruhiko Kikuchi ◽  
Kouzo Moritake ◽  
Seiichi Nagao ◽  
Kouichi Iwasaki ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Brain Tissue ◽  
Mouse Brain ◽  
Tumor Necrosis ◽  
Normal Mouse ◽  
Mononuclear Cell Infiltration ◽  
Content Type ◽  
Normal Mouse Brain ◽  
Necrosis Factor ◽  
Fine Print

✓ Morphological and ultrastructural changes in normal mouse brain tissue were investigated after intracerebral stereotactic injections of tumor necrosis factor (specific activity: 2.0 × 106 U/mg protein) into the right frontal lobe. The mice received either a single infusion or multiple tumor necrosis factor infusions in three different dose groups (10, 100, or 500 U). Compared with sham-treated control mice that received adjusted intracerebral injections of purified albumin, the tumor necrosis factor-treated mice in all dose groups did not show any specific in vivo behavioral abnormalities during the 2 months of study following the infusions. Histological studies revealed hemorrhage attributable to the mechanics of the intracerebral infusions, a thickening of the arachnoid membranes, a reactive gliosis, and neutrophilic and/or mononuclear cell infiltration along the infusion pathway. A local neutrophilic response was prominent 1 day after tumor necrosis factor injection. An immunohistochemical analysis indicated that the mononuclear cell infiltration consisted of lymphocytes and macrophages. Except for the transient neutrophilic infiltration, these histological alterations did not differ from those seen in the sham-treated control groups, and most nonspecific reactive changes disappeared within 8 weeks after the injections. Furthermore, an ultrastructural study showed no apparent pathological changes in the cytoplasmic organelles of neuronal, glial, and endothelial cells in the tumor necrosis factor-injected mouse specimens. These results suggest that the tumor necrosis factor injections caused no specific toxicity and did not alter the parenchymal and stromal cells comprising normal mouse brain tissue.

Flavonoid fraction from chayote (Sechium edule (Jacq.) Sw) leaves reduced malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in hyperuricemic rats

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Aulia Putri Wahyuningtyas ◽  
Diah Pitaloka Putri ◽  
Nani Maharani ◽  
Ahmad Ni'matullah Al-Baarri
Keyword(s):  
Oxidative Stress ◽  
Tumor Necrosis Factor ◽  
Inflammatory Markers ◽  
Tumor Necrosis ◽  
Oxidative Stress Marker ◽  
Content Type ◽  
Sechium Edule ◽  
Short Period ◽  
Flavonoid Fraction ◽  
Necrosis Factor

Purpose This paper aims to study the effect of the flavonoid fraction of chayote (Sechium edule (Jacq.) Sw) leaves (FFCL) on uric acid (UA) levels, oxidative stress and inflammatory markers in hyperuricemia rats. Design/methodology/approach In total, 30 Sprague–Dawley rats were divided randomly into 5 groups. A healthy control group was established. Hyperuricemia was induced by the administration of block broth and potassium oxonate for three weeks. FFCL at dosages of 50 and 100 mg/200 g BW/d or allopurinol at a dosage of 1.8 mg/200 g BW/d was given orally for 2 weeks. Statistical analysis was conducted to evaluate differences among groups before and after the intervention. Findings Treatment with two different doses FFCL (50 and 100 mg/200 g BW/d) and one dose of allopurinol (1.8 mg/200 g BW/d) for 2 weeks significantly reduced UA from 8.04 ± 0.23 to 3.88 ± 0.10; 8.03 ± 0.18 to 2.87 ± 0.10; 8.23 ± 0.21 to 2.53 ± 0.19 (p < 0.05), respectively. The oxidative stress marker malondialdehyde levels were reduced (p = 0.001) from 9.68 ± 0.28 to 4.06 ± 0.58; 10.01 ± 0.23 to 2.12 ± 0.09; 9.88 ± 0.21 to 2.02 ± 0.17 (p = 0.001). The inflammatory marker tumor necrosis factor-α (TNF-α) levels were also reduced from 26.43 ± 0.87 to 12.20 ± 0.32; 27.38 ± 0.53 to 9.60 ± 0.53; 27.55 ± 0.68 to 8.83 ± 0.21 with p = 0.001. The 100 mg/200 g BW/d FFCL decreased UA levels, oxidative stress and inflammatory markers more extensively compared to 50 mg/200 g BW/d FFCL. Research limitations/implications This study includes some limitations that may affect the generalizability of its findings. First, the flavonoid levels of FFCL were not measured. Second, other oxidative stress biomarkers (e.g. superoxide dismutase) and inflammatory biomarkers (e.g. IL-6) were not investigated. Finally, the experiments were conducted on the model animals over a relatively short period of time. Further research is needed to evaluate the effect in humans at chronic use. Practical implications Chayote (Sechium edule (Jacq.) Sw) leaves are rich in flavonoids, especially apigenin and luteolin, which can improve oxidative stress and inflammation conditions caused by hyperuricemia. Social implications Hyperuricemia is a risk factor for non-communicable diseases, mostly caused by oxidative stress and inflammation in the body due to high levels of UA, one of the treatment strategies is through diet modification. Originality/value The results of this investigation imply that the administration of the flavonoid fraction of chayote leaves has significant effects on UA and oxidative stress and inflammatory markers. Further research is necessary to confirm the results.

scholarly journals Differential Gamma Interferon- and Tumor Necrosis Factor Alpha-Driven Cytokine Response Distinguishes Acute Infection of a Metatherian Host with Toxoplasma gondii and Neospora caninum

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Shannon L. Donahoe ◽  
David N. Phalen ◽  
Bronwyn M. McAllan ◽  
Denis O'Meally ◽  
Milton M. McAllister ◽  
...  
Keyword(s):  
Immune Response ◽  
Toxoplasma Gondii ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Neospora Caninum ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Toxoplasma gondii and Neospora caninum (both Apicomplexa) are closely related cyst-forming coccidian parasites that differ significantly in their host ranges and ability to cause disease. Unlike eutherian mammals, Australian marsupials (metatherian mammals) have long been thought to be highly susceptible to toxoplasmosis and neosporosis because of their historical isolation from the parasites. In this study, the carnivorous fat-tailed dunnart (Sminthopsis crassicaudata) was used as a disease model to investigate the immune response and susceptibility to infection of an Australian marsupial to T. gondii and N. caninum. The disease outcome was more severe in N. caninum-infected dunnarts than in T. gondii-infected dunnarts, as shown by the severity of clinical and histopathological features of disease and higher tissue parasite burdens in the tissues evaluated. Transcriptome sequencing (RNA-seq) of spleens from infected dunnarts and mitogen-stimulated dunnart splenocytes was used to define the cytokine repertoires. Changes in mRNA expression during the time course of infection were measured using quantitative reverse transcription-PCR (qRT-PCR) for key Th1 (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), Th2 (interleukin 4 [IL-4] and IL-6), and Th17 (IL-17A) cytokines. The results show qualitative differences in cytokine responses by the fat-tailed dunnart to infection with N. caninum and T. gondii. Dunnarts infected with T. gondii were capable of mounting a more effective Th1 immune response than those infected with N. caninum, indicating the role of the immune response in the outcome scenarios of parasite infection in this marsupial mammal.

Clinical effect of intra-arterial tumor necrosis factor-α for malignant glioma

1992 ◽  
Vol 77 (1) ◽  
pp. 78-83 ◽  
Author(s):  
Jun Yoshida ◽  
Toshihiko Wakabayashi ◽  
Masaaki Mizuno ◽  
Kenichiro Sugita ◽  
Tazuka Yoshida ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Malignant Glioma ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tumor Regression ◽  
Malignant Gliomas ◽  
Human Tumor ◽  
Content Type ◽  
Factor Α ◽  
Necrosis Factor

✓ Recombinant human tumor necrosis factor-α was administered intra-arterially to treat 20 cases of malignant gliomas, mostly progressive or recurrent. The optimum dosage was determined to be 1 × 105 U/sq m/day. Among the 10 evaluable patients treated at this dosage, two responded (one completely and one partially), resulting in a 20% response rate. Side effects were mild and easily controllable. Improvement of neurological symptoms was noted in 47% of the patients a few days after treatment, even when computerized tomography showed no tumor regression. This might have been due to the pleiotypic biological activity of tumor necrosis factor-α. Neuroradiographic observations revealed narrowing of the tumor-feeding artery, a decrease in tumor staining ability, and necrosis in the central part of a tumor. The authors suggest that intra-arterial administration of tumor necrosis factor-α may be an effective treatment for malignant glioma, including recurrent cases.

scholarly journals Tumor Necrosis Factor Alpha Modulates the Dynamics of the Plasminogen-Mediated Early Interaction between Bifidobacterium animalis subsp.lactisand Human Enterocytes

2012 ◽  
Vol 78 (7) ◽  
pp. 2465-2469 ◽  
Author(s):  
Manuela Centanni ◽  
Simone Bergmann ◽  
Silvia Turroni ◽  
Sven Hammerschmidt ◽  
Gursharan Singh Chhatwal ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Bifidobacterium Animalis ◽  
Factor Alpha ◽  
Open Question ◽  
Early Interaction ◽  
Necrosis Factor

ABSTRACTThe capacity to intervene with the host plasminogen system has recently been considered an important component in the interaction process betweenBifidobacterium animalissubsp.lactisand the human host. However, its significance in the bifidobacterial microecology within the human gastrointestinal tract is still an open question. Here we demonstrate that human plasminogen favors theB. animalissubsp.lactisBI07 adhesion to HT29 cells. Prompting the HT29 cell capacity to activate plasminogen, tumor necrosis factor alpha (TNF-α) modulated the plasminogen-mediated bacterium-enterocyte interaction, reducing the bacterial adhesion to the enterocytes and enhancing migration to the luminal compartment.

Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury

2005 ◽  
Vol 82 (5) ◽  
pp. 701-716 ◽  
Author(s):  
Albert Quintana ◽  
Mercedes Giralt ◽  
Santiago Rojas ◽  
Milena Penkowa ◽  
Iain L. Campbell ◽  
...  
Keyword(s):  
Brain Injury ◽  
Tumor Necrosis Factor ◽  
Mouse Brain ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Tumor Necrosis Factor Receptors ◽  
Necrosis Factor

Expression of Nuclear Factor κB and Tumor Necrosis Factor α in the Mouse Brain after Experimental Thermal Ablation Injury

Neurosurgery ◽  
2001 ◽  
Vol 48 (1) ◽  
pp. 158-166 ◽  
Author(s):  
Yasuyuki Nomoto ◽  
Masaaki Yamamoto ◽  
Takeo Fukushima ◽  
Hideo Kimura ◽  
Kohichi Ohshima ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Mouse Brain ◽  
Thermal Ablation ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Vitamin D Rescues Impaired Mycobacterium tuberculosis-Mediated Tumor Necrosis Factor Release in Macrophages of HIV-Seropositive Individuals through an Enhanced Toll-Like Receptor Signaling PathwayIn Vitro

2012 ◽  
Vol 81 (1) ◽  
pp. 2-10 ◽  
Author(s):  
Asha Anandaiah ◽  
Sanjeev Sinha ◽  
Medhavi Bole ◽  
Surendra K. Sharma ◽  
Narendra Kumar ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis Factor ◽  
Alveolar Macrophages ◽  
Tumor Necrosis ◽  
Nuclear Translocation ◽  
Content Type ◽  
Human Macrophages ◽  
Hiv Seropositive ◽  
Necrosis Factor

Mycobacterium tuberculosisdisease represents an enormous global health problem, with exceptionally high morbidity and mortality in HIV-seropositive (HIV+) persons. Alveolar macrophages from HIV+persons demonstrate specific and targeted impairment of critical host cell responses, including impairedM. tuberculosis-mediated tumor necrosis factor (TNF) release and macrophage apoptosis. Vitamin D may promote anti-M. tuberculosisresponses through upregulation of macrophage NO, NADPH oxidase, cathelicidin, and autophagy mechanisms, but whether vitamin D promotes anti-M. tuberculosismechanisms in HIV+macrophages is not known. In the current study, human macrophages exposed toM. tuberculosisdemonstrated robust release of TNF, IκB degradation, and NF-κB nuclear translocation, and these responses were independent of vitamin D pretreatment. In marked contrast, HIV+U1 human macrophages exposed toM. tuberculosisdemonstrated very low TNF release and no significant IκB degradation or NF-κB nuclear translocation, whereas vitamin D pretreatment restored these critical responses. The vitamin D-mediated restored responses were dependent in part on macrophage CD14 expression. Importantly, similar response patterns were observed with clinically relevant human alveolar macrophages from healthy individuals and asymptomatic HIV+persons at high clinical risk ofM. tuberculosisinfection. Taken together with the observation that local bronchoalveolar lavage fluid (BALF) levels of vitamin D are severely deficient in HIV+persons, the data from this study demonstrate that exogenous vitamin D can selectively rescue impaired critical innate immune responsesin vitroin alveolar macrophages from HIV+persons at risk forM. tuberculosisdisease, supporting a potential role for exogenous vitamin D as a therapeutic adjuvant inM. tuberculosisinfection in HIV+persons.

scholarly journals Group B Streptococcus and Streptococcus suis Capsular Polysaccharides Induce Chemokine Production by Dendritic Cells via Toll-Like Receptor 2- and MyD88-Dependent and -Independent Pathways

2013 ◽  
Vol 81 (9) ◽  
pp. 3106-3118 ◽  
Author(s):  
Cynthia Calzas ◽  
Guillaume Goyette-Desjardins ◽  
Paul Lemire ◽  
Fleur Gagnon ◽  
Claude Lachance ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Capsular Polysaccharides ◽  
Toll Like Receptor ◽  
Chemokine Production ◽  
Content Type ◽  
Toll Like Receptor 2 ◽  
Group B ◽  
Necrosis Factor

ABSTRACTStreptococcus agalactiae(also known as group BStreptococcus[GBS]) andStreptococcus suisare encapsulated streptococci causing severe septicemia and meningitis. Bacterial capsular polysaccharides (CPSs) are poorly immunogenic, but anti-CPS antibodies are essential to the host defense against encapsulated bacteria. The mechanisms underlying anti-CPS antibody responses are not fully elucidated, but the biochemistry of CPSs, particularly the presence of sialic acid, may have an immunosuppressive effect. We investigated the ability of highly purifiedS. suisand GBS native (sialylated) CPSs to activate dendritic cells (DCs), which are crucial actors in the initiation of humoral immunity. The influence of CPS biochemistry was studied using CPSs extracted from different serotypes within these two streptococcal species, as well as desialylated CPSs. No interleukin-1β (IL-1β), IL-6, IL-12p70, tumor necrosis factor alpha (TNF-α), or IL-10 production was observed inS. suisor GBS CPS-stimulated DCs. Moreover, these CPSs exerted immunosuppressive effects on DC activation, as a diminution of gamma interferon (IFN-γ)-induced B cell-activating factor of the tumor necrosis factor family (BAFF) expression was observed in CPS-pretreated cells. However,S. suisand GBS CPSs induced significant production of CCL3, via partially Toll-like receptor 2 (TLR2)- and myeloid differentiation factor 88 (MyD88)-dependent pathways, and CCL2, via TLR-independent mechanisms. No major influence of CPS biochemistry was observed on the capacity to induce chemokine production by DCs, indicating that DCs respond to these CPSs in a patterned way rather than a structure-dedicated manner.

scholarly journals Brucella abortus Invasion of Osteocytes Modulates Connexin 43 and Integrin Expression and Induces Osteoclastogenesis via Receptor Activator of NF-κB Ligand and Tumor Necrosis Factor Alpha Secretion

2015 ◽  
Vol 84 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Ayelén Ivana Pesce Viglietti ◽  
Paula Constanza Arriola Benitez ◽  
María Virginia Gentilini ◽  
Lis Noelia Velásquez ◽  
Carlos Alberto Fossati ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Brucella Abortus ◽  
Connexin 43 ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Receptor Activator ◽  
Factor Alpha ◽  
Necrosis Factor

Osteoarticular brucellosis is the most common localization of human active disease. Osteocytes are the most abundant cells of bone. They secrete factors that regulate the differentiation of both osteoblasts and osteoclasts during bone remodeling. The aim of this study is to determine ifBrucella abortusinfection modifies osteocyte function. Our results indicate thatB. abortusinfection induced matrix metalloproteinase 2 (MMP-2), receptor activator for NF-κB ligand (RANKL), proinflammatory cytokines, and keratinocyte chemoattractant (KC) secretion by osteocytes. In addition, supernatants fromB. abortus-infected osteocytes induced bone marrow-derived monocytes (BMM) to undergo osteoclastogenesis. Using neutralizing antibodies against tumor necrosis factor alpha (TNF-α) or osteoprotegerin (OPG), RANKL's decoy receptor, we determined that TNF-α and RANKL are involved in osteoclastogenesis induced by supernatants fromB. abortus-infected osteocytes. Connexin 43 (Cx43) and the integrins E11/gp38, integrin-α, integrin-β, and CD44 are involved in cell-cell interactions necessary for osteocyte survival.B. abortusinfection inhibited the expression of Cx43 but did not modify the expression of integrins. Yet the expression of both Cx43 and integrins was inhibited by supernatants fromB. abortus-infected macrophages.B. abortusinfection was not capable of inducing osteocyte apoptosis. However, supernatants fromB. abortus-infected macrophages induced osteocyte apoptosis in a dose-dependent manner. Taken together, our results indicate thatB. abortusinfection could alter osteocyte function, contributing to bone damage.

scholarly journals Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) Mediates Ubiquitination-Dependent STAT3 Activation upon Salmonella enterica Serovar Typhimurium Infection

2017 ◽  
Vol 85 (8) ◽  
Author(s):  
Hai-Hua Ruan ◽  
Zhen Zhang ◽  
Su-Ying Wang ◽  
Logan M. Nickels ◽  
Li Tian ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Salmonella Enterica ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Effector Proteins ◽  
Host Cells ◽  
Associated Factor ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Necrosis Factor

ABSTRACT Salmonella enterica serovar Typhimurium can inject effector proteins into host cells via type III secretion systems (T3SSs). These effector proteins modulate a variety of host transcriptional responses to facilitate bacterial growth and survival. Here we show that infection of host cells with S. Typhimurium specifically induces the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). This TRAF6 ubiquitination is triggered by the Salmonella pathogenicity island 1 (SPI-1) T3SS effectors SopB and SopE2. We also demonstrate that TRAF6 is involved in the SopB/SopE2-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), a signaling event conducive to the intracellular growth of S. Typhimurium. Specifically, TRAF6 mediates lysine-63 ubiquitination within the Src homology 2 (SH2) domain of STAT3, which is an essential step for STAT3 membrane recruitment and subsequent phosphorylation in response to S. Typhimurium infection. TRAF6 ubiquitination participates in STAT3 phosphorylation rather than serving as only a hallmark of E3 ubiquitin ligase activation. Our results reveal a novel strategy in which S. Typhimurium T3SS effectors broaden their functions through the activation of host proteins in a ubiquitination-dependent manner to manipulate host cells into becoming a Salmonella-friendly zone.

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