149 PRODUCTION OF KNOCK-DOWN MICE WITH shRNA CYTOCHROME P-450 4F16 GENE AND REDUCTION OF THE IMMUNE SYSTEM

2012 ◽  
Vol 24 (1) ◽  
pp. 187
Author(s):  
B. C. Yang ◽  
K. C. Hwang ◽  
K. W. Kim ◽  
H. C. Lee ◽  
H. J. Chung ◽  
...  
Keyword(s):  
Immune System ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Wild Type ◽  
Knock Down ◽  
Tnf Α ◽  
C57bl Mice ◽  
Mrna And Protein Expression ◽  
Factor Α ◽  
Cytochrome P 450

The putative mouse homologue of cytochrome P-450 4F16 (Cyp4f16) is induced by interleukin-1 (Il-1), interleukin-6 (Il-6) and tumour necrosis factor-α (Tnf-α) and repressed by interleukin-10 (Il-10) and lipopolysaccharide (LPS). The Cyp4F16 is a subfamily of Cyp4F and it is also related to eicosanoids that are important mediators in the inflammatory cascade (Cui et al. 2001). To investigate the role of Cyp4F16, in the present study, we report the production of Cyp4f16 gene knock-down mice in 2 strains of mice, namely A/J and C57BL/6. The A/J is susceptible to infection and it is associated with Cyp4F16, whereas C57BL/6 is relatively resistant to infection. An shRNA-Cyp4F16 expression vector was microinjected into pronuclei of fertilized mouse oocytes and the embryos were transferred into pseudopregnant recipients. As a result, 25 and 50 mice were produced in the A/J and C57BL, respectively. Two mice in the A/J strain and 6 in the C57BL strain were confirmed by PCR as transgenic. Organs were collected in each of the lines produced by inbreeding and screened with real-time PCR for Cyp4f16 transcripts. The Cyp4f16 gene was expressed in a tissue-specific manner with high expression in the pancreas, spleen and lung and a lower level of transcription in the heart, muscle, thymus, kidney, testis and liver. In the spleen of transgenic Cyp4f16 knock-down mice, Cyp4f16 mRNA and protein expression levels were significantly lower than those of wild-type mice. The A/J Cyp4f16 knock-down mice suffered an inflammatory skin disease and tumours, but wild-type A/J mice and knock-down C57BL mice did not. Taken together, these results suggest that Cyp4f16 may play a regulatory role in the immune system and point to the use of the Cyp4f16 knock-down mouse as an experimental animal model for the study of the inflammatory process. This work was supported by a grant PJ0070762010 from BioGreen 21 Program, Rural Development Administration, Republic of Korea.

Predisposition to Hyperthyroidism May Be Influenced by Functional TNF-α, IL-1, IL-6, and IL-10 Polymorphisms: A Meta-Analysis

2020 ◽  
Vol 181 (12) ◽  
pp. 956-965
Author(s):  
Hong Ma ◽  
Ting Tan ◽  
Jie Wu ◽  
Juan Chen ◽  
Xiaohong Zhang
Keyword(s):  
Meta Analysis ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Asian Origin ◽  
Tnf Α ◽  
Caucasian Origin ◽  
Meta Analyses ◽  
Factor Α ◽  
Necrosis Factor

<b><i>Background:</i></b> Predisposition to hyperthyroidism may be influenced by functional gene polymorphisms in tumor necrosis factor-α (<i>TNF-α</i>), interleukin-1 (<i>IL-1</i>), interleukin-4 (<i>IL-4</i>), interleukin-6 (<i>IL-6</i>), and interleukin-10 (<i>IL-10</i>). However, the results of the studies published so far remain discrepant, so we conducted a meta-analysis to more robustly investigate relationships between <i>TNF-α</i>/<i>IL-1/IL-4/IL-6/IL-10</i> polymorphisms and predisposition to hyperthyroidism. <b><i>Methods:</i></b> A comprehensive literature retrieval from PubMed, Embase, Web of Science, WanFang, VIP, and CNKI was endorsed by the authors, and 38 studies were found to be eligible for pooled meta-analyses. <b><i>Results:</i></b> We found that genotypic frequencies of <i>TNF-α</i> −308 G/A, <i>IL-1A</i> −889 C/T, <i>IL-6</i> −174 G/C, <i>IL-6</i> −572 G/C, <i>IL-10</i> −819 C/T, and <i>IL-10</i> −1082 A/G polymorphisms among cases were significantly different from those among controls. Moreover, we also found that genotypic frequencies of <i>TNF-α</i> −308 G/A and <i>IL-6</i> −174 G/C polymorphisms among cases of Caucasian origin were significantly different from those among Caucasian controls, and genotypic frequencies of <i>IL-1A</i> −889 C/T, <i>IL-1B</i> −511 C/T, <i>IL-6</i> −174 G/C, <i>IL-6</i> −572 G/C, and <i>IL-10</i> −1,082 A/G polymorphisms among cases of Asian origin were also significantly different from those among Asian controls. <b><i>Conclusions:</i></b> This meta-analysis suggests that <i>TNF-α</i> −308 G/A, <i>IL-1A</i> −889 C/T, <i>IL-1B</i> −511 C/T, <i>IL-6</i> −174 G/C, <i>IL-6</i> −572 G/C, <i>IL-10</i> −819 C/T, and <i>IL-10</i> −1,082 A/G polymorphisms may influence predisposition to hyperthyroidism in certain ethnic groups.

scholarly journals The effects of chrysin on cypermethrin-induced acute intoxication in rainbow trout (Oncorhynchus mykiss)

2019 ◽  
Vol 27 (2) ◽  
pp. 102-111
Author(s):  
Ozge Cerit ◽  
Feride Koc
Keyword(s):  
Interleukin 1 ◽  
Interleukin 10 ◽  
Control Group ◽  
Interleukin 1 Beta ◽  
Tissue Samples ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Tnf Α ◽  
Factor Α ◽  
Oxidative Effects ◽  
Necrosis Factor

Abstract Cypermethrin (CP) is a toxic insecticide to fishes. Chrysin (CR) is a flavonoid, which can be obtained from plants. The aim of this study was to determine the effects of CR in fishes that had acute CP toxicity. In the study, a total of 60 fishes were used and added to feed and water with CR and CP for 10 days. Blood and tissue samples were collected. The serum enzymes aspartate transaminase (AST) and alanine aminotransferase (ALT), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels/activities were determined for liver and kidneys. In this study, when the CP group was compared to the control group, an increase was observed in the levels/activities of AST, ALT, IL-1ß, TNF-α, and IL-6, otherwise, there was a decrease in the IL-10 level in the CP group. Additionally, an increase of MDA levels and a decrease of SOD, GSH-Px, and CAT levels/activities were observed in the CP group. When the CP group was compared to the CR groups, there was a decrease in IL-1β, IL-6, TNF-α, ALT, AST, and MDA levels/activities and there was an increase, depending on the dosage in GSH-Px, SOD, and CAT levels/activities of the CR groups. In conclusion, CR can prevent tissue damage, affecting oxidation via anti-inflammatory and anti-oxidative effects of acute toxicity of fishes exposed to CP.

Contributions of angiotensin II and tumor necrosis factor-α to the development of renal fibrosis

2001 ◽  
Vol 280 (5) ◽  
pp. F777-F785 ◽  
Author(s):  
Guangjie Guo ◽  
Jeremiah Morrissey ◽  
Ruth McCracken ◽  
Timothy Tolley ◽  
Helen Liapis ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Tumor Necrosis Factor ◽  
Renal Fibrosis ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Wild Type ◽  
Tnf Α ◽  
Factor Α ◽  
Tgf Β1 ◽  
Necrosis Factor

Angiotensin II upregulates tumor necrosis factor-α (TNF-α) in the rat kidney with unilateral ureteral obstruction (UUO). In a mouse model of UUO, we found that tubulointerstitial fibrosis is blunted when the TNF-α receptor, TNFR1, is functionally knocked out. In this study, we used mutant mice with UUO in which the angiotensin II receptor AT1a or the TNF-α receptors TNFR1 and TNFR2 were knocked out to elucidate interactions between the two systems. The contribution of both systems to renal fibrosis was assessed by treating TNFR1/TNFR2-double knockout (KO) mice with an angiotensin-converting enzyme inhibitor, enalapril. The increased interstitial volume (Vvint) in the C57BI/6 wild-type mouse was decreased in the AT1a KO from 32.8 ± 4.0 to 21.0 ± 3.7% ( P < 0.005) or in the TNFR1/TNFR2 KO to 22.3 ± 2.1% ( P < 0.005). The Vvint of the TNFR1/TNFR2 KO was further decreased to 15.2 ± 3.7% ( P < 0.01) by enalapril compared with no treatment. The induction of TNF-α mRNA and transforming growth factor-β1 (TGF-β1) mRNA in the kidney with UUO was significantly blunted in the AT1a or TNFR1/TNFR2 KO mice compared with the wild-type mice. Treatment of the TNFR1/TNFR2 KO mouse with enalapril reduced both TNF-α and TGF-β1 mRNA and their proteins to near normal levels. Also, α-smooth muscle actin expression and myofibroblast proliferation were significantly inhibited in the AT1a or TNFR1/TNFR2 KO mice, and they were further inhibited in enalapril-treated TNFR1/TNFR2 KO mice. Incapacitating the angiotensin II or the TNF-α systems individually leads to partial blunting of fibrosis. Incapacitating both systems, by using a combination of genetic and pharmacological means, further inhibited interstitial fibrosis and tubule atrophy in obstructive nephropathy.

scholarly journals Atherosclerosis as Pathogenetic Substrate for Sars-Cov2 Cytokine Storm

2020 ◽  
Vol 9 (7) ◽  
pp. 2095 ◽  
Author(s):  
Mattia Vinciguerra ◽  
Silvia Romiti ◽  
Khalil Fattouch ◽  
Antonio De Bellis ◽  
Ernesto Greco
Keyword(s):  
Immune System ◽  
Viral Replication ◽  
Multiorgan Failure ◽  
Severe Infection ◽  
Adverse Outcomes ◽  
Alveolar Cells ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Plasmatic Concentration

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) outbreak is a public health emergency affecting different regions around the world. The lungs are often damaged due to the presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection varies from complete absence of symptomatology to more aggressive symptoms, characterized by sudden acute respiratory distress syndrome (ARDS), multiorgan failure, and sepsis, requiring treatment in intensive care unit (ICU). It is not still clear why the immune system is not able to efficiently suppress viral replication in a small percentage of patients. It has been documented as pathological conditions affecting the cardiovascular system, strongly associated to atherosclerotic progression, such as heart failure (HF), coronary heart disease (CHD), hypertension (HTN) and diabetes mellitus (DM), could serve as predictive factors for severity and susceptibility during Sars-CoV-2 infection. Atherosclerotic progression, as a chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory patterns, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1β. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results reported in severe COVID-19 infections, we hypothesized a pathogenetic correlation. Atherosclerosis may be an ideal pathogenetic substrate for high viral replication ability, leading to adverse outcomes, as reported in patients with cardiovascular factors. The level of atherosclerotic progression may affect a different degree of severe infection; in a vicious circle, feeding itself, Sars-CoV-2 may exacerbate atherosclerotic evolution due to excessive and aberrant plasmatic concentration of cytokines.

Tumor necrosis factor-α and interleukin-1 β levels in recurrent and persistent otitis media with effusion

2002 ◽  
Vol 126 (4) ◽  
pp. 417-422 ◽  
Author(s):  
Sertac Yetiser ◽  
Bulent Satar ◽  
Atilla Gumusgun ◽  
Faruk Unal ◽  
Yalcin Ozkaptan
Keyword(s):  
Tumor Necrosis Factor ◽  
Otitis Media ◽  
Tumor Necrosis ◽  
Otitis Media With Effusion ◽  
Interleukin 1 ◽  
Tertiary Referral Center ◽  
Adenoid Tissue ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

OBJECTIVE: Based on interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels in effusions, our goals were to specify either recurrent or persistent otitis media with effusion (OME) is a mid stage in the development of chronic disease and to identify the factors that have an influence on cytokine levels. STUDY DESIGN: Samples from groups with recurrent (n = 15) and persistent (n = 39) OME were essayed for IL-1 β and TNF-α. Children were also grouped with respect to age, sex, quality of effusion, and the presence of pharyngeal adenoid tissue. SETTING: Tertiary referral center. RESULTS: In recurrent and persistent OME groups, IL-1β was higher than TNF-α ( P < 0.01). IL-β was higher in recurrent OME than in persistent OME ( P < 0.05). CONCLUSION: Recurrent OME seems to be closer to the chronic stage of the disease relative to persistent OME in terms of higher IL-1 β levels. Each exacerbation of acute disease in recurrent otitis media is likely to be mediated by IL-1 β. SIGNIFICANCE: We were able to clarify that recurrent OME is a stage that occurs before chronic OME. Therefore, the prevention of acute attacks in recurrent disease would also impede long-term damage to the middle ear.

scholarly journals Epileptogenesis due to glia-mediated synaptic scaling

2008 ◽  
Vol 6 (37) ◽  
pp. 655-668 ◽  
Author(s):  
Cristina Savin ◽  
Jochen Triesch ◽  
Michael Meyer-Hermann
Keyword(s):  
Immune System ◽  
Neuronal Activity ◽  
Activity Patterns ◽  
Brain Inflammation ◽  
Network Activity ◽  
Homeostatic Regulation ◽  
Synaptic Scaling ◽  
Tnf Α ◽  
Factor Α ◽  
Potential Interactions

Homeostatic regulation of neuronal activity is fundamental for the stable functioning of the cerebral cortex. One form of homeostatic synaptic scaling has been recently shown to be mediated by glial cells that interact with neurons through the diffusible messenger tumour necrosis factor-α (TNF-α). Interestingly, TNF-α is also used by the immune system as a pro-inflammatory messenger, suggesting potential interactions between immune system signalling and the homeostatic regulation of neuronal activity. We present the first computational model of neuron–glia interaction in TNF-α-mediated synaptic scaling. The model shows how under normal conditions the homeostatic mechanism is effective in balancing network activity. After chronic immune activation or TNF-α overexpression by glia, however, the network develops seizure-like activity patterns. This may explain why under certain conditions brain inflammation increases the risk of seizures. Additionally, the model shows that TNF-α diffusion may be responsible for epileptogenesis after localized brain lesions.

Increased cytochrome P-450 2E1 expression sensitizes hepatocytes to c-Jun-mediated cell death from TNF-α

2002 ◽  
Vol 282 (2) ◽  
pp. G257-G266 ◽  
Author(s):  
Hailing Liu ◽  
Brett E. Jones ◽  
Cynthia Bradham ◽  
Mark J. Czaja
Keyword(s):  
Cell Death ◽  
Oxidant Stress ◽  
Nuclear Factor Κb ◽  
Dominant Negative ◽  
Tnf Α ◽  
Cyp2e1 Expression ◽  
Factor Α ◽  
Jnk Activation ◽  
Cytochrome P 450 ◽  
Necrosis Factor

The mechanisms underlying hepatocyte sensitization to tumor necrosis factor-α (TNF-α)-mediated cell death remain unclear. Increases in hepatocellular oxidant stress such as those that occur with hepatic overexpression of cytochrome P-450 2E1 (CYP2E1) may promote TNF-α death. TNF-α treatment of hepatocyte cell lines with differential CYP2E1 expression demonstrated that overexpression of CYP2E1 converted the hepatocyte TNF-α response from proliferation to apoptotic and necrotic cell death. Death occurred despite the presence of increased levels of nuclear factor-κB transcriptional activity and was associated with increased lipid peroxidation and GSH depletion. CYP2E1-overexpressing hepatocytes had increased basal and TNF-α-induced levels of c-Jun NH2-terminal kinase (JNK) activity, as well as prolonged JNK activation after TNF-α stimulation. Sensitization to TNF-α-induced cell death by CYP2E1 overexpression was inhibited by antioxidants or adenoviral expression of a dominant-negative c-Jun. Increased CYP2E1 expression sensitized hepatocytes to TNF-α toxicity mediated by c-Jun and overwhelming oxidative stress. The chronic increase in intracellular oxidant stress created by CYP2E1 overexpression may serve as a mechanism by which hepatocytes are sensitized to TNF-α toxicity in liver disease.

The Augmented Productions of Neopterin and Cytokines from Macrophages/monocytes in vitro

Pteridines ◽  
1996 ◽  
Vol 7 (3) ◽  
pp. 72-76
Author(s):  
Tadashi Lizuka ◽  
Mitsuyo Sasaki ◽  
Hitomi Kamisako ◽  
Ko Oishi ◽  
Shigeru Uemura ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Interleukin 1 ◽  
Poly I:C ◽  
Recombinant Interferon ◽  
Preliminary Examination ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Summary In Kawasaki disease patients, increases in excretion of urinary neopterin coincided with fever and monocytosis in peripheral blood. We examined the products of neopterin, tumor necrosis factor-α (TNFα) and Interleukin-1 β (1L-1β) from healthy adult macrophages/monocytes (Mφ>/M), after stimulation with several activators to obtain some understanding of Kawasaki disease. Upon stimulation with either lipopolysaccharide (LPS) or polyinosinate-polycytidylate (Poly I:C), the Mφ/M released neopterin and pyogenic products (TNF-α or 1L-1β). The release of neopterin was eliminated by the addition of the anti-interferon-y antibody. The production of both TNF-α, 1L-1β and neopterin from Mφ/M upon stimulation of LPS was augmented in a co-culture with low dose recombinant interferon-y (rIFN-γ). Upon stimulation with rIFN-γ alone, however, the Mφ/M released neopterin but not the pyogenic products. A preliminary examination failed to detect. any difference in the response of the Mφ/M in adults annd children after stimulation with LPS. We concluded that some endotoxins could trigger the onset of Kawasaki disease and that endogenous IFN-γ can play an important role in the abnormality of Kawasaki disease patients

Acute Immunomodulatory Effects of Fentanyl and its Three New Analogues in Swiss Albino Mice

2017 ◽  
Vol 3 (1) ◽  
pp. 24 ◽  
Author(s):  
Shiv Kumar Yadav ◽  
Rahul Bhattacharya
Keyword(s):  
Pain Management ◽  
Opioid Receptor ◽  
Inflammatory Cytokines ◽  
Opioid Analgesic ◽  
Interleukin 10 ◽  
Acute Effect ◽  
Post Exposure ◽  
Tnf Α ◽  
Pre Treatment ◽  
Factor Α

Fentanyl is a potent synthetic opioid analgesic. However, due to its several limitations, new analogues are being synthesised for better pain management. We have earlier reported the synthesis and bio-efficacy of fentanyl and its eight new analogues (1-8) in mice. Among eight analogues tested, N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) were found to be more effective and less toxic compared to fentanyl. Therapeutic efficacy of fentanyl and its analogues are known to be compromised due to many adverse effects, including alterations in the immune system. Therefore, the present study was undertaken to assess the acute effect of fentanyl and its three analogues (2, 5, and 6) on plasma levels of different pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and anti-inflammatory cytokines such as interleukin-10 (IL-10) at different time points. Mice were intraperitoneally treated with 0.50 LD50 of the compounds and cytokines were measured 1 h, 2 h, 4 h, and 24 h post-exposure. Compared to control, none of the treatments produced any change in TNF-α and IL-1β levels. However, IL-6 levels were significantly elevated between 1 h to 2 h post-exposure in fentanyl and analogue 2 treated groups. Further, IL-10 levels were found to be significantly increased in fentanyl, analogue 2, and 6 treated groups at 1 h and 2 h post-exposure. Pre-treatment of naltrexone (opioid receptor antagonist) blocked the effects of fentanyl, confirming that its effects were opioid receptor- dependent. However, effect of naltrexone on analogue 2 and 6 was not conclusively evidenced, indicating that immunomodulatory changes caused by the analogues could have some additional implications as well. The present study reveals undesirable effects of fentanyl and its new analogues on cytokines homeostasis, thereby limiting their use in pain management.

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