Role Of Tumor Necrosis Factor-α Research Articles

TNF-α Levels Are Increased in Patients with Subjective Cognitive Impairment and Are Negatively Correlated with β Amyloid-42.

The role of tumor necrosis factor-α (TNF-α) in Alzheimer's disease (AD) has recently become a topic of debate. TNF-α levels increase in the blood of patients with AD, and amyloid beta (Aβ) plaques contain TNF-α deposits. The therapeutic efficacy of blocking TNF-α in patients with AD remains controversial as it is mostly based on preclinical studies. Thus, whether and how TNF-α contributes to amyloidogenic processes in AD is still an open question to be addressed. We analyzed plasma TNF-α and Aβ42 levels in patients with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), and AD, and in healthy volunteers (HLT). In addition, we performed correlation analysis to evaluate whether changes in plasma TNF-α levels correlate with cognitive decline, Aβ42 levels, age, and BMI, which are all factors considered to contribute to or predispose individuals to AD. We found that TNF-α and Aβ42 plasma levels were higher in patients with AD than in HLT individuals. High TNF-α levels were also observed in patients with SCI, in whom TNF-α and Aβ42 levels were negatively correlated. Notably, TNF-α did not affect the amyloidogenic pathway in human microglial cultures exposed to 48 h of incubation, although it did trigger neuroinflammatory processes. These results imply that high TNF-α levels are more likely to be a clinical condition linked to AD than are direct contributors. Nonetheless, elevated levels of TNF-α in early-stage patients, like those with SCI and MCI, may provide a distinguishing feature for identifying clinical profiles that are at risk of having a poorer outcome in AD and could benefit from tailored therapies.

Effect of Serum Breadfruit Leaf Extract (Artocarpus Altilis) on TNF-Α and Sod Levels (Experimental Study on Guinea Pigs Exposed to UVB Light)

Continuous exposure to ultraviolet B (UVB) light can increase the amount of melanin, causing hyperpigmentation on the skin. This process involves the important role of Tumor Necrosis Factor-α (TNF-α) and Superoxide Dismutase (SOD). Artocarpus Altilis contain flavonoids that have anti-inflammatory potential, can reduce TNF-α levels and increase SOD which affects the melanogenesis process. To determine the effect of administering Artocarpus Altilis extract serum on TNF-α and SOD levels in guinea pigs exposed to UVB. This research is an in vivo experimental study with Post Test Only Group design, which was conducted at the IBL FK Laboratory (Integrated Biomedical Laboratory Faculty of Medicine) Unissula. A total of 30 male guinea pigs were divided into 5 groups, namely: Group 1 sham, group 2 negative control, group 3 treated with 2% Artocarpus Altilis extract serum, group 4 treated with 4% serum and group 5 treated with 6% serum. Then analyzed using the One-way ANOVA test to determine differences between groups. The lowest mean TNF-α levels were found in group P2 (4.958), other values were P1 (5.820), P3 (5.964), KS (6.069) and KN (5.811). Meanwhile, the average SOD levels in all groups were not much different, P2 (5.802), P1 (5.975), P3 (5.906), KS (6.054) and KN (6.000). In the One-way ANOVA test on TNF-α and SOD there was no significant difference, p>0.05. Administration Artocarpus Altilis extract serum, especially 4%, caused a decrease in TNF-α levels but was not significant, and there was no increase in SOD levels, in guinea pigs exposed to UVB light.

Ly-6A-Induced Growth Inhibition and Cell Death in a Transformed CD4+ T Cell Line: Role of Tumor Necrosis Factor-α.

Ly-6A, a member of the Ly-6/uPAR supergene family of proteins, is a cell adhesion and cell signaling protein. Signaling through Ly-6A activates the cell-intrinsic apoptotic cell death pathway in CD4+ T cell lines, as indicated by the release of cytochrome C, and activation of caspases 9 and 3. In addition, Ly-6A induces cytokine production and growth inhibition. The mechanism underlying the distinct cellular responses that are triggered by engaging Ly-6A protein has remained unknown. To examine the relatedness of these distinct responses, we have quantified the production of pro-apoptotic, growth inhibitory and tumor suppressive cytokines, such as TNF-α, TGF-β and a related protein GDF-10, in response to Ly-6A signaling. Anti-Ly-6A monoclonal antibody-induced activation of YH16.33 CD4+ T cell line generated low levels of TGF-β and GDF-10 but elevated levels of TNF-α. Blocking the biological activity of TNF-α resulted in reduced Ly-6A-induced apoptosis in T cells. The Ly-6A-induced response in the T cell line was distinct, as signaling through the antigen receptor complex did not cause growth inhibition and apoptosis despite high levels of TGF-β and GDF-10 that were detected in these cultures. Additionally, in response to antigen receptor complex signaling, lower amount of TNF-α was detected. These results indicate the contribution of TNF-α in the observed Ly-6A-induced growth inhibition and apoptosis and provide a mechanistic explanation for the biologically distinct responses observed in CD4+ T cells after engaging Ly-6A protein. Additionally, the findings reported here will aid in the understanding of inhibitory signaling initiated by Ly-6A protein, especially in the context of its potential immune checkpoint inhibitory role in T cells.

TNF-α AND IONIZING RADIATION: THE ROLE IN THE PATHOGENESIS AND TREATMENT OF PLASMA CELL MYELOMA (review).

The review presents data from the literature on the role of Tumor necrosis factor-α (TNF-α) and ionizing radiation (IR) in the pathogenesis and treatment of plasma cell myeloma (PCM). There was analyzed disturbance of regulation of functioning of this cytokine, which affects the interaction of the immune system with substrate plasma cells under the influence of negative external factors, including ionizing radiation IR. Modern directions of therapy of this disease using the latest technologies are presented, in particular CAR T-cell therapy, which will allow to optimize in the future treatment of this disease and, thus, improve the quality and life expectancy of PCM patients.

Relationship between mucosal TNF-α expression and Th1, Th17, Th22 and Treg responses in Helicobacter pylori infection

Helicobacter pylori (H. pylori)-induced gastric inflammation in the gastric mucosa and significantly increases the risk of developing gastritis and peptic ulcer disease (PUD). The objective of this research is to determine the role of tumor necrosis factor-α (TNF-α) expression in the gastric mucosa of patients with H. pylori-associated gastritis and PUD compared to uninfected patients, and we determined the relation between TNF-α expression and Th1/Th17/Th22, and Treg cells. Fifty-five patients with H. pylori-associated gastritis, 47 patients with H. pylori-associated PUD, and 48 uninfected patients were in this research. Antrum biopsy was used to detect H. pylori, virulence factors and histopathological assessments. Expression of TNF-α in the infected group was significantly higher than the uninfected group. Also, cagA/oipA-positive infected patients induce significantly more TNF-α expression than do cagA/oipA-negative infected patients. Expression of TNF-α was significantly increased in the PUD group than the gastritis group. Notably, TNF-α expression had a significant positive correlation with the frequency of Th1/Th17/Th22 lymphocytes in the PUD group. These findings indicate the importance of increasing TNF-α with Th1, Th17, Th22 responses increase as an important risk factor for PUD in context of H. pylori infection.

069 Role of tumor necrosis factor-α and soluble tumor necrosis factor-α receptor-1 in the formation of oligomenorhea in adolescent girls with obesity

Introduction: In recent years, the role of adipose tissue producing pro-inflammatory cytokines involved in the regulation of immunity and reproduction has been actively studied. In this regard, it is relevant to study the immune mechanisms of the formation of ovarian dysfunction in adolescent girls with obesity.

The Levels of TNF-α, Tissue Factor, and Coagulation Function in Rats with Pulmonary Hypertension and the Intervention Effect of Sildenafil Encapsulated by Targeted Nanocarriers.

Pulmonary hypertension (PAH) is a proliferative disease of pulmonary blood vessels, but the pathogenesis of pulmonary hypertension is still unclear. This article explores the role of tumor necrosis factor-α (TNF-α), tissue factor (TF), and coagulation function (CF) in the pathogenesis of PAH. PAH is often accompanied by vascular intima injury and muscular arterial media thickening. Coupled with the wide application of nanotargeted drugs in recent years, a targeted nanocarrier encapsulating sildenafil was prepared in this study. The particle size, PDI, zeta potential, drug loading, and encapsulation efficiency were 194.32 ± 17.31 nm, 0.28 ± 0.02, −6.34 ± 0.33, 24.61%, and 70.52%. The monocrotaline PAH rat model was constructed, and it was found that the levels of TNF-α, TF, and CF in the peripheral blood of PAH rats were abnormally increased. 30 PAH rats were randomly divided into 5 groups and injected with saline (NS group), sildenafil (sildenafil group), target the nanoempty carrier (TNC-E group), ordinary nanocarrier encapsulated sildenafil (CNC-sildenafil group), and targeted nanocarrier encapsulate sildenafil (TNC-sildenafil group). Compared with the NS group, the mean pulmonary artery pressure in the TNC-sildenafil group was lower (P < 0.05). Compared with the normal rat group, the pulmonary small blood vessel media thickness, TNF-α level, TF level, and the area of myocardial cells were increased in the NS group, sildenafil group, TNC-E group, and CNC-sildenafil group (P < 0.05). Compared with the NS group, the pulmonary small blood vessel media thickness, myocardial cell area, and the levels of TNF-α and TF in the TNC-sildenafil group were reduced (P < 0.05). Targeting nanocarrier encapsulation of sildenafil can obviously reduce the average pulmonary artery pressure in rats with pulmonary hypertension, improve pulmonary vascular media proliferation and myocardial hypertrophy, and restore the levels of TNF-α, TF, and CF to a normal state.

Modafinil exerts anticonvulsive effects against lithium-pilocarpine-induced status epilepticus in rats: A role for tumor necrosis factor-α and nitric oxide signaling

BackgroundStatus epilepticus (SE) is a continuous episode of seizures which leads to hippocampal neurodegeneration, severe systemic inflammation, and extreme damage to the brain. Modafinil, a psychostimulant and wake-promoting agent, has exerted neuroprotective and anti-inflammatory effects in previous preclinical studies. The aim of this study was to assess effects of modafinil on the lithium-pilocarpine-induced SE rat model and to explore possible involvement of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) pathways in this regard. MethodsStatus epilepticus was provoked by injection of lithium chloride (127 mg/kg, intraperitoneally [i.p]) and pilocarpine (60 mg/kg, i.p.) in rats. Animals received different modafinil doses (50, 75, 100, and 150 mg/kg, i.p.) and SE scores were documented over 3 hours of duration. Moreover, the role of the nitrergic pathway in the effects of modafinil was evaluated by injection of the non-selective NO synthase (NOS) inhibitor L-NG-Nitro arginine methyl ester (L-NAME, 10 mg/kg, i.p.), the selective neuronal NOS inhibitor 7-nitroindazole (30 mg/kg, i.p.), and the selective inducible NOS inhibitor aminoguanidine (100 mg/kg, i.p.) 15 min before saline/vehicle or modafinil. The ELISA method was used to quantify TNF-α and NO metabolite levels in the isolated hippocampus. ResultsModafinil at 100 mg/kg significantly decreased SE scores (P < 0.01). Pre-treatment with L-NAME, 7-nitroindazole, and aminoguanidine significantly reversed the anticonvulsive effects of modafinil. Status epilepticus-induced animals showed significantly higher NO metabolite and TNF-α levels in their hippocampal tissues, an effect that was reversed by modafinil (100 mg/kg, i.p.) treatment. Administration of NOS inhibitors resulted in excessive NO level reduction but an escalation of TNF-α level in modafinil-treated SE-animals. ConclusionOur study revealed anticonvulsive effects of modafinil in the lithium-pilocarpine-induced SE rat model via possible involvement of TNF-α and nitrergic pathways.

The Potential Predictive Role of Tumour Necrosis Factor-α, Interleukin-1β, and Monocyte Chemoattractant Protein-1 for COVID-19 Patients Survival.

BackgroundTumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) are early phase cytokines often encountered when the body is exposed to severe acute respiratory syndrome-associated-coronavirus-2. TNF-α, IL-1β, and MCP-1 are pro-inflammatory cytokines critical in the defence response against systemic infection and injury. Therefore, TNF-α, IL-1β, and MCP-1 are the most aggressive responses to viral infections in the acute phase, so they can be used to determine the survival of coronavirus disease 2019 (COVID-19) patients.PurposeThe study aimed to determine the levels of TNF-α, IL-1β, and MCP-1 as predictors of survival for COVID-19 patients.Patients and MethodsA prospective cohort study was conducted on confirmed COVID-19 by a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) in 84 adults admitted to the hospital in Indonesia. TNF-α, IL-1β, and MCP-1 level were measured from serum subjects using the enzyme-linked immunosorbent assay.ResultsThe results from logistic regression modelling of the survival status of COVID-19 patients based on TNF-α, IL-1β, and MCP-1 levels were significant (p-value=0.024). The predictors of all cytokines had P Wald <0.05, so the three cytokines could be used simultaneously to predict the survival status of COVID-19 patients. MCP-1 has the most dominant risk relative value (2.76; 95% CI; 2.53–4.68) compared to TNF-α and IL-1β in predicting patient survival.ConclusionTNF-α, IL-1β, and MCP-1 as markers of acute systemic inflammatory cytokines can be measured at the beginning of hospitalisation of COVID-19 patients for early diagnosis of disease severity so that healthcare professionals can determine clinical guidance needs for therapeutic programs.

Neuroinflammation as a mechanism linking hypertension with the increased risk of Alzheimer’s disease

Alzheimer’s disease, the most common type of dementia among older adults, currently cannot be prevented or effectively treated. Only a very small percentage of Alzheimer’s disease cases have an established genetic cause. The majority of Alzheimer’s disease cases lack a clear causative event, but several modifiable factors have been associated with an increased risk of this disease. Persistent midlife hypertension is one such risk factor, which can be effectively controlled through changes in diet, lifestyle, and antihypertensive drugs. Identifying molecular mechanisms linking modifiable risk factors with the increased risk of Alzheimer’s disease could enhance our understanding of this disease and lead to identification of novel targets and therapeutic approaches for effective treatments. Glial cell-driven neuroinflammation is one of the key pathological features of Alzheimer’s disease. In this review, we illustrate that neuroinflammation could also be one of the possible mechanisms linking hypertension and Alzheimer’s disease. Animal studies have demonstrated that chronically elevated blood pressure leads to adverse glial activation and increased brain inflammatory mediators. We highlight damage to cerebral microvasculature and locally activated renin-angiotensin system as the key pathogenetic mechanisms linking hypertension to neuroinflammation and the accompanying neurodegeneration. The role of tumor necrosis factor-α and interleukin-1β as pro-inflammatory signaling molecules providing this link is discussed. We also summarize the available experimental data indicating that neuroinflammatory changes and glial activation can be reversed by several different classes of antihypertensive medicines. These studies suggest antihypertensives could be beneficial in Alzheimer’s disease not only due to their ability to control the blood pressure, but also due to their anti-neuroinflammatory effects. Confirmation of these observations in human subjects is required and recent advances in the brain imaging techniques allowing visualization of both microglia and astrocyte activation will be essential for this research.

Association of Genetic Polymorphism of Tumor Necrosis Factor-α in the Development of Coronary Heart Disease in Elderly Patients

The research project outlines a new look at the concept of "inflammaging" and the role of the subclinical inflammatory process in various age-associated pathology, in particular coronary heart disease. Particular attention is paid to the tumor necrosis factor-α -cytokine, which plays an important role in the pathogenesis of chronic inflammatory processes and in the aging process. The increased content of tumor necrosis factor-α leads to the emergence and accumulation of various diseases, disability and mortality of elderly and senile people.&#x0D; Tumor necrosis factor-α influences various risk factors for cardiovascular pathology. This substance aggravates various breakdowns in metabolism, primarily causing insulin resistance. Tumor necrosis factor-α is a key cytokine that stimulates bone resorption (osteoporosis) and sarcopenia. Currently available data prove the important role of tumor necrosis factor-α in various age-associated pathologies.

Roles of Tumor Necrosis Factor-α and Tumor Necrosis Factor-α Receptor 2 in Inflammation-Related Diseases

The aim of the present review is to provide basic knowledge about the role of tumour necrosis factor-α 1 and tumor necrosis factor-α receptor 2 in neuro-inflammation diseases. We performed an open-ended, English restricted search of PubMed, Embase, PsychINFO, Web of Science, Scopus, and the Cochrane Library for available literature from 24Feb. 2018–12 May 2021, using terms related to neuroinflammation, tumour necrosis factor-α, tumour necrosis factor II (TNFR-II), TNF-α and related diseases, TNFR-II and inflammation-related diseases, their relationships, and polymorphism. The main outcomes assessed were the presence of plaques and tangles, behaviour and cognition, reduction in brain tissue mass, and synaptic function the majority of studies were documented a beneficial effect in other areas, including the presence of plaques and tangles and synaptic function. The human studies were showed that TNF-αI was beneficial to Alzheimer's disease patients, with one being a small pilot study and the latter being an observational study, with a high risk of bias. It is concluded that the functions and mechanisms of TNF-α and TNFR-II in inflammation-related diseases will provide new viewpoints and theories in the development and treatment of these diseases. They play important roles in the pathogenesis of diseases induced by or related to inflammatory cytokines and signaling pathways.

Role of tumor necrosis factor-α in the mortality of hospitalized patients with severe and critical COVID-19 pneumonia.

The coronavirus disease 2019 (COVID-19) is presently the most pressing public health concern worldwide. Cytokine storm is an important factor leading to death of patients with COVID-19. This study aims to characterize serum cytokines of patients with severe or critical COVID-19. Clinical records were obtained from 149 patients who were tested at the Sino-French New City Branch of Tongji Hospital from 30 January to 30 March 2020. Data regarding the clinical features of the patients was collected and analyzed. Among the 149, 45 (30.2%) of them had severe conditions and 104 (69.8%) of that presented critical symptoms. In the meantime, 80 (53.7%) of that 149 died during hospitalization. Of all, male patients accounted for 94 (69.1%). Compared with patients in severe COVID-19, those who in critical COVID-19 had significantly higher levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and IL-10. Moreover, the passed-away patients had considerably higher levels of TNF-α, IL-6, IL-8, and IL-10 than those survived from it. Regression analysis revealed that serum TNF-α level was an independent risk factor for the death of patient with severe conditions. Among the proinflammatory cytokines (IL-1β, TNF-α, IL-8, and IL-6) analyzed herein, TNF-α was seen as a risk factor for the death of patients with severe or critical COVID-19. This study suggests that anti-TNF-α treatment allows patients with severe or critical COVID-19 pneumonia to recover.

Role of tumor necrosis factor-α, interleukin-1β, interleukin-6 in liver inflammation in chronic hepatitis B and chronic hepatitis C

Role of tumor necrosis factor-α, interleukin-1β, interleukin-6 in liver inflammation in chronic hepatitis B and chronic hepatitis C

Retraction to: Mechanisms of Hemorrhage-Induced Hepatic Insulin Resistance: Role of Tumor Necrosis Factor-α.

Retraction to: Mechanisms of Hemorrhage-Induced Hepatic Insulin Resistance: Role of Tumor Necrosis Factor-α.

Tumor Necrosis Factor-Alpha and Age-Related Pathologies

Modern concepts about the «inflammaging» and the role of subclinical inflammation in various age-associated pathology are described in the review. Particular attention is paid to the tumor necrosis factor-α, a key cytokine that plays an important role in the pathogenesis of chronic inflammatory diseases as well as in aging. The increased levels of tumor necrosis factor-α leads to the onset and progression of various diseases, to severity of frailty, to disability and mortality of elderly persons. Tumor necrosis factor-α affects different risk factors for cardiovascular diseases, contributes to the onset and progression of atherosclerosis and related pathology. This cytokine can also aggravate various metabolic disorders, mainly — insulin resistance and diabetes mellitus. Tumor necrosis factor-α is a key cytokine that stimulates bone resorption (up to osteoporosis) and sarcopenia (up to cachexia). Currently available data confirm the important role of tumor necrosis factor-α in various age-associated disorders.

Tumor Necrosis Factor Receptor-1 (p55) Deficiency Attenuates Tumor Growth and Intratumoral Angiogenesis and Stimulates CD8+ T Cell Function in Melanoma.

The role of tumor necrosis factor-α (TNF-α) in shaping the tumor microenvironment is ambiguous. Consistent with its uncertain role in melanoma, TNF-α plays a dual role, either acting as a cytotoxic cytokine or favoring a tumorigenic inflammatory microenvironment. TNF-α signals via two cognate receptors, namely TNFR1 (p55) and TNFR2 (p75), which mediate divergent biological activities. Here, we analyzed the impact of TNFR1 deficiency in tumor progression in the B16.F1 melanoma model. Tumors developed in mice lacking TNFR1 (TNFR1 knock-out; KO) were smaller and displayed lower proliferation compared to their wild type (WT) counterpart. Moreover, TNFR1 KO mice showed reduced tumor angiogenesis. Although no evidence of spontaneous metastases was observed, conditioned media obtained from TNFR1 KO tumors increased tumor cell migration. Whereas the analysis of tumor-associated immune cell infiltrates showed similar frequency of total and M2-polarized tumor-associated macrophages (TAMs), the percentage of CD8+ T cells was augmented in TNFR1 KO tumors. Indeed, functional ex vivo assays demonstrated that CD8+ T cells obtained from TNFR1KO mice displayed an increased cytotoxic function. Thus, lack of TNFR1 attenuates melanoma growth by modulating tumor cell proliferation, migration, angiogenesis and CD8+ T cell accumulation and activation, suggesting that interruption of TNF-TNFR1 signaling may contribute to control tumor burden.

Role of tumor necrosis factor-α in Chlamydia Muridarum infection in the urogenital tract of mice

To explore the role of tumor necrosis factor-α (TNF-α) in immune response to urogenital chlamydial infection and urogenital pathology in mice. Fifteen female wild-type (WT) C57BL/6J mice and 15 TNF-α receptor knockout (TNF-αR KO) mice were inoculated intravaginally with 1×104 inclusion forming units (IFUs) of live C. muridarum. At 56 days after the first inoculation, 8 mice from each group were subjected to a second inoculation at the same dose. Vaginal swabs were taken every 3 or 4 days to detect the number of inclusion bodies of chlamydia. On day 80 after the first inoculation, the mice were euthanized and peritoneal macrophages were collected and the vaginal tract and spleen were dissected. The pathologies in the fallopian tube and the uterine horn were observed and the severity of inflammatory cell infiltration and lumen dilatation were semi-quantitatively scored. The levels of interleukin-6 (IL-6), IL-8, IL-1α, IL-1β and TNF-α in the supernatant of the peritoneal macrophage were detected. Spleen cell suspension was prepared, and after stimulation with chlamydia EB in vitro, the levels of the cytokines including IL-4, IL-5, IL-17 and interferon-γ (IFN-γ) were determined in the cells. The clearance rate of Chlamydia from the urogenital tract was similar between TNF-αR KO mice and WT mice regardless of the primary or second infection. The severity of inflammation in the fallopian tube and the uterine horn did not differ significantly between the two groups, but TNF-αR KO mice had significantly milder dilation of the fallopian tubes (P < 0.05). The peritoneal macrophages from TNF-αR KO mice produced a significantly higher level of TNF-α than those from WT mice (P < 0.05); the spleen cells from the two groups both produced high levels of IFN-γ, but IL-17 production by the spleen cells was significantly lower in TNF-αR KO mice than in WT mice (P < 0.05). TNF-α is not associated with protective immune response against C. muridarum infection, and can worsen the inflammatory damages of the urogenital tract caused by C. muridarum in mice.

Role of Tumor Necrosis Factor-α in vascular hyporeactivity following endotoxic shock and its mechanism.

Vascular hyporeactivity plays an important role in organ dysfunction induced by endotoxic shock. Given that cytokine, such as TNF-α, plays an important role in endotoxic shock, the aim of the present study is to investigate the role of Tumor Necrosis Factor (TNF)-α in vascular hyporeactivity following endotoxic shock and the mechanisms. Lipopolysaccharide (LPS) (1 mg/kg) injection was used for replicating the endotoxic shock model in the rabbit. The changes in the level of TNF-α in plasma in the rabbits model and the contractile response of superior mesenteric arteries (SMA) to norepinephrine (NE) and Ca were observed. The mechanisms in TNF-α-induced vascular hyporeactivity were further explored. The levels of TNF-α in plasma were gradually increased after 1 hour of LPS administration and reached the peak at 6 hours. The contractile responses of SMA to NE were decreased at 1 hour of LPS and lowest at 6 hour. TNF-α (200 ng/mL) incubation decreased contractile response of SMA to NE significantly. Further studies found that calcium desensitization participated in the occurrence of TNF-α-induced vascular hyporeactivity, the changes were consistent with the changes of vascular reactivity, calcium sensitivities were decreased significantly at 1 hour, 2 hours, 4 hours, and 6 hours after LPS injection. TNF-α (200 ng/mL) incubation could significantly reduce the contractile response of SMA to Ca. The activity of Rho-kinase and the changes of myosin light chain 20 (MLC20) phosphorylation level were significantly decreased at 6 hours following LPS administration, and TNF-α (200 ng/mL) incubation led to a decrease of Rho-kinase and MLC20 phosphorylation. Arginine vasopressin significantly antagonized TNF-α (200 ng/mL)-induced the decrease of the vascular reactivity and calcium sensitivity. TNF-α is involved in vascular hyporeactivity after endotoxic shock. Calcium desensitization plays an important role in TNF-α-induced vascular hyporeactivity after endotoxic shock. Rho-kinase/MLC20 phosphorylation pathway takes part in the regulation of calcium desensitization and vascular hyporeactivity induced by TNF-α. Arginine vasopressin is beneficial to endotoxic shock in TNF-α-induced vascular hyporeactivity.

Protective effects of probiotics on acute alcohol-induced liver injury in mice through alcohol metabolizing enzymes activation and hepatic TNF-α response reduction

Abstract Purpose The role of tumor necrosis factor-α (TNFα) and toll-like receptor 4 (TLR 4) in the pathogenesis of alcoholic liver disease (ALD) has been widely entrenched. We investigated the profitable effects of Bifidobacterium bifidum YRT3115 and Bifidobacterium animalis subsp. lactis KV9 on tumor necrosis factor-α (TNFα) expression and injury response to acute alcohol gavage in mice. Methods Ninety-six C57BL/6 mice were classified into 4 groups: control, intragastric administration of white spirit, intragastric administration of white spirit + YRT3115 and intragastric administration of white spirit + KV9. The mice were treated daily with probiotics and white spirit until 15 days. The body weight, food intake, liver weight and liver index of mice were measured. Duration of alcohol-induced loss of righting reflex (LORR) was also evaluated. The concentration of ethanol (EtOH) and acetaldehyde (AcH) in mice blood were performed by a head-space GC. The activity of aspartate transaminase (AST) and alanine transaminase (ALT) in mice serum, activity of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in mice liver were performed by commercial kits. The liver mRNA levels of TNF-α, CYP2E1 and TLR 4 were evaluated by RT-PCR. The protein level of TNF-α was evaluated by Western-blot. Results After intragastric administration white spirit, B. animalis subsp. lactis KV9 reduced duration of LORR, recovery of loss of righting reflex (RORR) and was significantly reduced the concentration of EtOH in blood of mice, by 15.69% at 30 min, 15.01% at 60 min and 45.01% at 120 min (p Conclusion This paper demonstrated that B. animalis subsp. lactis KV9 supplementation reduced markedly hepatic inflammation, liver injury and improve alcohol metabolism, but B. bifidum YRT3115 was not. These results suggested firmly that treatment with B. animalis subsp. lactis KV9 could potential ameliorate liver from the injury of alcohol.