tnf - tumor necrosis factor
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Pubmed
Journal: International journal of immunogenetics
November/27/2006
Abstract
Graft-versus-host disease (GvHD) is the main complication after haematopoietic stem cells transplantation (HSCT) and acute forms (aGvHD) occur in 20-40% of cases even after donor (D) and recipient (R) HLA matching, apparently because of D/R minor histocompatibility antigen (mHA) mismatches and cytokine polymorphisms. The genotype of cytokines and mHA of 77 haematological R following HSCT from HLA identical siblings were determined to detect genetic polymorphisms correlated with GvHD. We analysed TNFA (-863 C/A, -857 C/T and G/A at positions -574, -376, -308, -244, -238), IL-10 (-1082 G/A, -819 C/A, -592 C/T), IL-1B (T/C +3953), IL-1RA (VNTR), HA-1 (H/R allele) and CD-31 (C/G at codon 125, A/G at codon 563). Allele frequencies were in Hardy-Weinberg equilibrium and similar to those of 77 healthy controls. We observed positive correlations between a lower risk of clinically significant aGvHD and both the presence of -1082G -819C -592C IL-10 haplotype when both R and D are considered together and the absence of R IL-1RA allele 2. Furthermore, we observed an association between the absence of TNF-A -238 A allele and the risk of extensive chronic GvHD. mHA and cytokines genotyping would thus seem a valid source of information for the prior identification of recipients with a higher risk of aGvHD.
Pubmed
Journal: The Journal of steroid biochemistry and molecular biology
March/5/2009
Abstract
We previously demonstrated that the expression of Mullerian inhibiting substance (MIS) in Sertoli cells is downregulated by tumor necrosis factor alpha (TNF-alpha), which is secreted by meiotic germ cells, in mouse testes. Several studies have reported that MIS that is secreted by Sertoli cells inhibits steroidogenesis and, thus, the synthesis of testosterone in testicular Leydig cells. Here, we demonstrate that in TNF-alpha knockout testes, which show high levels of MIS, steroidogenesis is decreased compared to that in wild-type testes. The levels of testosterone and the mRNA levels of steroidogenesis-related genes were significantly lower after puberty in TNF-alpha knockout testes than in wild-type testes. Furthermore, the number of sperm was reduced in TNF-alpha knockout mice. Histological analysis revealed that spermatogenesis is also delayed in TNF-alpha knockout testes. In conclusion, TNF-alpha knockout mice show reduced testicular steroidogenesis, which is likely due to the high level of testicular MIS compared to that seen in wild-type mice.
Pubmed
Journal: British journal of haematology
December/5/2010
Abstract
Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1β were observed in cITP (P < 10(-3) ) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL-2 and γ-interferon (IFN-γ) were increased in cITP patients (P < 10(-3) and P = 0·04 respectively) and blood donors (P < 10(-3) and P = 0·03 respectively) harbouring the IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.
Pubmed
Journal: Human immunology
January/2/2007
Abstract
To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) gene as susceptibility marker for spondyloarthritis (SpA), two polymorphisms (-238 and -308 positions) were analyzed in 229 patients with SpA (113 with ankylosing spondylitis [AS], 92 with undifferentiated SpA [U-SpA], 24 with reactive arthritis), and 169 ethnically matched healthy control subjects. The HLA-B alleles were detected by PCR-SSP technique and the TNF-alpha polymorphism by PCR-RFLP. In comparison with healthy control subjects, the frequencies of TNF-238 in SpA were similar. In contrast, the analysis of -308 polymorphism showed increased frequencies of the T2(A) allele in the whole SpA group (p < 0.05, pC = NS, OR = 1.83) as well as the T2(A) allele (pC < 0.05, OR = 2.4) and T1T2(AG) genotype (p < 0.05, pC = NS, OR = 2.25) in U-SpA patients. Comparison of B27-negative patients and healthy control subjects yielded similar results. There was no significant correlation between TNF genotypes and clinical data. The present study demonstrates that TNF-alpha -308 polymorphism appears to be associated with the genetic susceptibility U-SpA. The association seems independent of the susceptibility conferred by the HLA-B27 in this group of patients.
Pubmed
Journal: Multiple sclerosis (Houndmills, Basingstoke, England)
October/13/2011
Abstract
BACKGROUND
Environmental and genetic factors are thought to be involved in the pathogenesis of multiple sclerosis (MS). Polymorphisms of tumor necrosis factor (TNF)-α -308 were implicated in MS risk in several case-control association studies. However, the studies have shown inconsistent results.
OBJECTIVE
To address the association of G/A polymorphisms of TNF-α -308 with MS risk by meta-analysis.
METHODS
Thirteen studies were included. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated.
RESULTS
A total of 1870 cases and 2769 controls were included in the meta-analysis. The pooled result indicated that -308 A allele is significantly associated with reduced risk of MS compared with -308 G allele (A vs. G, p=0.022). The same pattern of the result was also obtained in the contrasts of AA+ GA vs. GG (p=0.008) and GA vs. GG (p=0.007). For AA vs. GG or AA vs. GA + GG, no significant association was detected most likely caused by very low frequency or non-availability of homozygote genotype AA for all of the studies.
CONCLUSIONS
TNF-α -308 A allele is associated with reduced risk of MS.
Pubmed
Journal: Clinical biochemistry
February/7/2017
Abstract
BACKGROUND
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. The biology of this disease remains elusive. In the present times, targeted molecular therapy defines the treatment. This has made understanding the elusive biology and molecular mechanisms of the disease more relevant. MicroRNAs (miRNAs) are non-encoding RNAs that play important gene-regulatory roles in neoplastic processes. As in silico studies list nearly hundreds and more target genes for each miRNA, it is of interest to see if there are genes that have already been implicated in this disease.
OBJECTIVE
The purpose of this study was to identify genes regulated by miRNAs that are independently implicated in the pathogenesis of CLL in previously published literature.
METHODS
Eight miRNAs were selected. Genes implicated in the biology of CLL in association studies and massively parallel sequence studies were selected. TargetScanHuman 6.2, a computational program that predicts target genes of miRNAs on the basis of sequence analysis, was used to link the miRNAs to genes of interest.
RESULTS
The genes targeted by miR-15a, miR-223, miR-29a, and miR181a included IL10RA, BCL2, BCL6, DDX3X, and FBXW7. The most significant link observed was that several gene members of the TNF/TNFR superfamily were targets of miR-15a, miR-29a, and miR-181a.
CONCLUSIONS
MiRNAs implicated in the pathogenesis of CLL regulate genes that have independently been shown to play a role in CLL. The link between miRNAs and the TNF/TNFR superfamily is especially exciting. Understanding the molecular basis of these links in future studies may pave the way for using these miRNAs as therapeutic targets in CLL.
Pubmed
Journal: International heart journal
November/28/2018
Abstract
Ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) is one of the deubiquitinating enzymes in the ubiquitin-proteasome system. It has been shown that UCH-L1 could markedly decrease neointima formation through suppressing vascular smooth muscle cell (VSMC) proliferation in the balloon-injured rat carotid. However, whether UCH-L1 plays roles in VSMC migration remains to be determined. In this study, the primary VSMCs were isolated from aortic media of rats and TNF-α to was used to induce VSMC migration. Using a modified Boyden chamber and wound healing assay, it was found that TNF-α can dose and time-dependently induce VSMC migration with a maximal effect at 10 ng/mL. Moreover, UCH-L1 expression increased gradually with the prolonged induction time at 10 ng/mL of TNF-α. UCH-L1 content in VSMC was then modulated by recombinant adenoviruses expressing UCH-L1 or RNA interference to evaluate its roles in cell migration. The results showed that over-expression of UCH-L1 attenuated VSMC migration, while knockdown of it enhanced cell migration significantly no matter whether TNF-α treatment or not. Finally, the effect of UCH-L1 on NF-κB activation was demonstrated by NF-κB nuclear translocation and DNA binding activity, and the levels of IL-6 and IL-8 in cell culture media were examined by ELISA. It was showed that UCH-L1 over-expression inhibited NF-κB activation and decrease IL-6 and IL-8 levels, while knockdown of it enhanced NF-κB activation and increase IL-6 and IL-8 levels during TNF-α treatment. These data suggest that UCH-L1 can inhibit TNF-α-induced VSMCs migration, and this kind of effect may partially due to its suppression role in NF-κB activation.
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Pubmed
Journal: Acta biochimica et biophysica Sinica
November/6/2012
Abstract
Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the relationship between functional polymorphisms of TNF-α and different outcomes of persistent HBV infection in a northeast Chinese Han population. Here 189 HBV spontaneously recovered subjects (SR), 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC), and 195 hepatocellular carcinoma (HCC) individuals were enrolled in this study. All the samples were genotyped for TNF-α -857C/T and -863C/A using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of -857CC genotype was significantly higher in CHB and LC individuals compared with that of SR subjects (P= 0.03, OR = 1.57, 95% CI 1.04-2.39 and P= 0.03, OR = 1.57, 95% CI 1.04-2.35, respectively). A significant difference in the distribution of the allele -857C was observed for both CHB vs. SR (P= 0.01, OR = 1.52, 95% CI 1.08-2.13) and LC vs. SR (P= 0.02, OR = 1.47, 95% CI 1.06-2.04) cohorts. In addition, the frequency of -863AA genotype was significantly higher in CHB and LC patients than that of SR subjects (P= 0.01, OR = 3.90, 95% CI 1.35-11.23 and P= 0.01, OR = 3.83, 95% CI 1.34-10.96, respectively), and allele -863A frequency was significantly more common in CHB, LC, and HCC cohorts than that of SR controls (P= 0.004, OR = 1.72, 95% CI 1.19-2.50; P= 0.001, OR = 1.81, 95% CI 1.26-2.61 and P= 0.001, OR = 1.90, 95% CI 1.33-2.73, respectively). Our data also revealed that haplotype CA was strongly associated with persistent HBV infection. These results suggest an association between the TNF-α promoter variants and different outcomes of persistent HBV infection in the studied population.
Pubmed
Journal: Gene
August/9/2012
Abstract
OBJECTIVE
Tumor necrosis factor alpha (TNF-α) is a major proinflammatory cytokine involved in the etiology of pancreatitis. The association between pancreatitis and the -308G>A and -238G>A polymorphisms in TNF-α gene has been analyzed in several studies, but results have been inconsistent. The purpose of this study was to integrate previous findings and explore whether these polymorphisms are associated with susceptibility and severity to pancreatitis.
METHODS
A meta-analysis was performed by searching PubMed, Cochrane Library, and ScienceDirect databases. Data were extracted using predefined form and odds ratios (OR) with 95% confidence intervals (CI) were calculated.
RESULTS
Our meta-analysis of a total of 1569 pancreatitis cases and 1330 control subjects from twelve published case-control studies for the -308G>A polymorphism (OR 0.98; 95% CI 0.83-1.17), and of 480 cases and 302 controls from four studies for the -238G>A polymorphism (OR 0.92; 95% CI 0.58-1.47) did not show any significant associations of susceptibility to pancreatitis with the variant GA+AA genotypes compared with the GG genotype. An association between severity of acute pancreatitis and -308G>A polymorphism was not found either (OR 0.93; 95% CI 0.69-1.24).
CONCLUSIONS
Polymorphisms in two sites of TNF-α gene promoter do not alter the risk of pancreatitis.
Pubmed
Journal: Hong Kong medical journal = Xianggang yi xue za zhi
December/20/2009
Abstract
1. The IFN-gamma +874A allele and RANTES -28 G allele are risk factors for SARS susceptibility. 2. The RANTES -28 G allele plays a role in the pathogenesis of SARS. 3. The polymorphisms of IL-10, TNF-alpha, IL-12, IP-10, Mig and MCP-1 are not associated with SARS susceptibility.
Pubmed
Journal: Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
June/7/2010
Abstract
OBJECTIVE
To explore the protective mechanisms of glycine (Gly) on lipopolysaccharides (LPS) induced liver injury.
METHODS
BABL/c mice were randomly divided into a LPS group, in which the animals were intraperitoneally injected with 10 mg/kg LPS, and a Gly group, in which the mice were pretreated with a 5% Gly-containing diet for 3 days before receiving the same dose of LPS. The livers of the mice were examined for histopathological changes. The TNF alpha and interleukin-10 (IL-10) levels in the blood plasma were measured using ELISA analysis. The mRNA expression of TNF alpha, IL-10 and Toll-like receptor 4 (TLR4) in hepatic tissues were detected using RT-PCR analysis. Protein expression of TLR4 in livers was detected using immunohistochemistry.
RESULTS
The Gly group mice had an improved survival rate and attenuated LPS-induced pathological changes in the liver tissues in comparison with those of the LPS group animals. The TNF alpha levels [(1,852.80+/-126.64) pg/ml vs (708.83+/-51.29) pg/ml, P<0.05] in plasma, as well as the expression of TNF alpha (A 1.59+/-0.14 vs. 0.91+/-0.11, P<0.05) and TLR4 (A 0.97+/-0.12 vs. 0.53+/-0.11, P<0.05) mRNA in liver tissues were decreased. However, the levels of plasma interleukin-10 [(344.09+/-31.70) pg/ml vs (418.64+/-38.86) pg/ml, P<0.05] were significantly increased and the peaking time left, shifted.
CONCLUSIONS
Gly pretreatment could attenuate LPS -induced liver injury in mice, which may be associated with its role in down-regulating TLR4 expression and up-regulating IL-10 production.
Pubmed
Journal: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
March/4/2017
Abstract
The proinflammatory cytokine tumour necrosis factor-alpha (TNFα) has long been characterized for its role in the innate immune system, but more recently has been found to have a distinct role in the nervous system that does not overlap with other proinflammatory cytokines. Through regulation of neuronal glutamate and GABA receptor trafficking, TNF mediates a homeostatic form of synaptic plasticity, but plays no direct role in Hebbian forms of plasticity. As yet, there is no evidence to suggest that this adaptive plasticity plays a significant role in normal development, but it does maintain neuronal circuit function in the face of several types of disruption. This includes developmental plasticity in primary sensory cortices, as well as modulating the response to antidepressants, chronic antipsychotics and drugs of abuse. TNF is also a prominent component of the neuroinflammation occurring in most neuropathologies, but the role of TNF-mediated synaptic plasticity in this context remains to be determined. We tested this in a maternal immune activation (MIA) model of neurodevelopmental disorders. Using TNF-/- mice, we observed that TNF is not required for the expression of abnormal social or anxious behaviour in this model. This indicates that TNF does not uniquely contribute to the development of neuronal dysfunction in this model, and suggests that during neuroinflammatory events, compensation between the various proinflammatory cytokines is the norm.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.
Pubmed
Journal: Cytokine
April/11/2010
Abstract
Bacterial infections can lead to a state of uncontrolled inflammation and also trigger autoimmune disease. At the centre of this are CD4(+) T cell responses in inflammatory tissues or local lymph nodes which are orchestrated by dendritic cells. IL-18 is a pro-inflammatory cytokine that drives dendritic cell maturation and mediates IFNgamma production. In this study, we demonstrate that in the dendritic precursor-like cell line KG-1, IFNgamma production induced by IL-18 is potentiated (>5-fold) by TNFalpha and completely suppressed by TGF-beta1. IL-18 stimulation rapidly activates different MAPK signalling pathways but only blocking of p38 activation alleviates IFNgamma production. The mechanism through which TNFalpha enhances IL-18 induced IFNgamma production is by promoting IL-18 receptor alpha-chain expression which results in higher levels of p38 activation and induces expression of T-bet, a transcriptional regulator of the IFNG gene. In contrast, TGF-beta1 rapidly suppresses IFNgamma production by limiting IL-18 receptor numbers at the cell surface and preventing induction of T-bet expression. TGF-beta1 experience by cells leads to sustained long-term inactivation of TNFalpha/IL-18-mediated cell activation but not IL-18 induced p38 activation suggesting transcriptional silencing of the T-BET and/or IFNG promoter independent of MAPK signalling. These results demonstrate how IL-18 activity is regulated by pro and anti-inflammatory cytokines and thereby provide insight into the mechanism that controls dendritic cell activity and ultimately leads to resolution of an inflammatory response.
Pubmed
Journal: International immunopharmacology
January/6/2014
Abstract
Inhibitor of apoptosis proteins (IAPs) contribute to both tumor progression and tumor metastasis. Here, we show that pro-inflammatory cytokine TNF-α induced the up-regulation of c-IAP2 in the potential metastatic nasopharyngeal carcinoma (NPC) cells in a dose- and time-dependent manner. This up-regulation is tolerant, as the pre-treatment of NPC cells with TNF-α reversed the up-regulation of c-IAP2 induced by TNF-α re-stimulation. TNF-α activated MAKP signals, including ERK, JNK and p38, and NF-κB signal, but only inhibition of JNK signal transduction reversed the induction of c-IAP2, suggesting that JNK signaling contributed to the c-IAP2 induction. The results from in vitro scratch wound-healing assays showed that TNF-α promoted cell invasion, which was reversed by the inhibition of JNK signaling. Taken together, these studies suggested that pro-inflammation cytokine TNF-α may be a promoter for NPC metastasis, and the anti-inflammatory therapy may be of benefit to the prevention of NPC metastasis.
Pubmed
Journal: Cytokine
August/26/2013
Abstract
Dendritic cells (DCs) and macrophages are effective antigen-presenting cells, and DCs, once matured, have the ability to potently activate naïve T cells. While the canonical p65/p50 NF-κB pathway seems to have an important role during LPS-stimulation of these cells, the specific contribution of the non-canonical RelB/p50 subunits is not clear yet. We aimed to investigate the relevance of this pathway in DCs and macrophages by using replication-deficient adenoviruses overexpressing RelB and p50 subunits to test their effect on cytokine production. In both cells, after LPS treatment, overexpression of RelB and p50 inhibited the production of some pro-inflammatory cytokines e.g., TNF, but not of others e.g. IL6. Anti-inflammatory IL10 was not affected. Moreover, when overexpressing p50 alone, IL10 was increased in LPS-activated macrophages. We thus demonstrated that the dimer RelB/p50 rather than the p50/p50 complex inhibits TNF production in LPS-stimulated DCs and macrophages. This implies that the non-canonical RelB/p50 could modulate the canonical p65/p50 pathway.
Pubmed
Journal: Inflammation
July/2/2008
Abstract
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine involved in mitogen-activated protein kinase (MAPK) signaling pathways, contributes to the pathogenesis of cardiovascular diseases. Recently, suppressor of cytokine signaling-1 (SOCS-1) has been shown to modulate responses to TNF-alpha. However, whether SOCS-1 suppresses TNF-alpha-dependent apoptotic processes in cardiomyocytes and whether MAPK pathways mediate this effect have not been clearly elucidated. This study was carried out to define the role of SOCS-1 on TNF-alpha-induced apoptosis in neonatal rat cardiomyocytes and to investigate the signal pathways involved. Exposure to TNF-alpha (10 ng/ml for 24 h) significantly increased the number of apoptotic cells, the activity of caspase-8 and caspase-3, and the Bax/Bcl-xl ratio. In contrast, adenovirus-mediated gene transfer of SOCS-1 reversed the pro-apoptotic effect of TNF-alpha. Additionally, preincubation of cardiomyocytes with the extracellular signal-regulated kinase-1 and -2 (ERK1/2) inhibitor PD98059 attenuated the protective effect of SOCS-1, but the p38-MAPK inhibitor SB203580 and the c-Jun amino-terminal kinase (JNK) inhibitor SP600125 had no effect. Furthermore, the TNF-alpha-induced decrease in the phosphorylation of ERK1/2 was abolished by overexpression of SOCS-1. These findings suggest that SOCS-1 prevents TNF-alpha-induced apoptosis in cardiac myocytes via ERK1/2 pathway activation.
Pubmed
Journal: Cellular signalling
June/2/2009
Abstract
TGF-beta regulates diverse biologic effects including cell growth, cell death or apoptosis, cell differentiation, and extracellular matrix (ECM) synthesis. Connective tissue growth factor (CTGF), induced by TGF-beta has been reported to mediate stimulatory action of TGF-beta-induced ECM. Although TNF-alpha was reported to suppress theTGF-beta-induced CTGF gene expression, the molecular mechanism is not well clarified. In this study, we found the inhibitory effect of TNF-alpha on TGF-beta-induced CTGF expression in WT but not p65-/-MEF cells. TNF-alpha neither induced Smad7 expression nor affected TGF-beta-induced Smad2 phosphorylation and nuclear translocation. We demonstrated that p300 physically associated with p65 rather than Smad4 in the presence of both TNF-alpha and TGF-beta. Moreover, the TGF-beta-induced binding of p300 and acetylated H4, but not Smad4 to the CTGF promoter was disturbed by TNF-alpha treatment. Overall, our data showed that suppression of TNF-alpha on TGF-beta-induced CTGF expression is due to the competition of p300 by p65 and Smad4.
Pubmed
Journal: PloS one
February/5/2012
Abstract
A number of inflammatory lung diseases have abnormally low glutathione (GSH) levels in the airway fluids. Lung macrophages are common mediators of inflammation, make up the majority of cells that are found in the airway epithelial lining fluid (ELF), and are commonly elevated in many lung diseases. Several animal models with altered ELF GSH levels are associated with similar alterations in the intracellular GSH levels of bronchoalveolar lavage (BAL) cells. The possible mechanisms and outcomes for this association between ELF GSH levels and intracellular BAL cell GSH are unknown. To investigate these issues, macrophages were grown in media supplemented with 500 µM GSH. GSH supplementation resulted in a 2-3 fold increase in macrophage intracellular GSH levels. The increase in macrophage intracellular GSH levels was associated with a significant reduction in NF-κB nuclear translocation and tumor necrosis factor α (TNFα) release upon LPS stimulation. Furthermore, co-treatment of macrophages with GSH and inhibitors of GSH breakdown or synthesis did not block GSH accumulation. In contrast, treatment with cytochalasin D, an inhibitor of actin dependent endocytosis, and amiloride, an inhibitor of macropinocytosis blocked, at least in part, GSH uptake. Furthermore, using two cigarette smoke exposure paradigms that result in two different GSH levels in the ELF and thus in the BAL cells resulted in modulation of cytokine release when stimulated with LPS ex vivo. These data suggest that macrophages are able to utilize extracellular GSH which can then modulate inflammatory signaling in response to proinflammatory stimuli. This data also suggests the lung can modulate inflammatory responses triggered by proinflammatory stimuli by altering ELF GSH levels and may help explain the dysregulated inflammation associated with lung diseases that have low ELF GSH levels.
Pubmed
Journal: Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology
March/9/2011
Abstract
OBJECTIVE
To detect the susceptible alleles in generalized aggressive periodontitis patients and healthy controls and to analyze the effect of multi-alleles on the occurrence and development of generalized aggressive periodontitis.
METHODS
Polymerase chain reaction and cleavage were used for detecting the frequencies of five susceptible genetic polymorphisms in generalized aggressive periodontitis patients and healthy controls. The results were analyzed by Z-score test and mean square analysis.
RESULTS
The frequencies of homozygous for HLA-DRB1* 1501 allele, TNF-A-308 allele II, IL-1B(+3953) allele II, vitamin D receptor allele A, T, estrogen receptor allele X in generalized aggressive periodontitis patients were higher than those in healthy controls. The persons who took more than three susceptible alleles (including three susceptible alleles) had more severe periodontal conditions than the ones who took less than three susceptible alleles (not including three susceptible alleles).
CONCLUSIONS
HLA-DRB1 * 1501 allele, TNFA-308 allele II, IL-1B(+3953) allele II, vitamin D receptor allele A, T, estrogen receptor allele X are susceptible alleles in generalized aggressive periodontitis. Carrying more than three susceptible alleles has a great effect on the occurrence and development of generalized aggressive periodontitis.
Pubmed
Journal: The European respiratory journal
June/25/2003
Abstract
Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). Tumour necrosis factor (TNF) family genes have been widely investigated but inconsistent results may lie either in the genetic heterogeneity of populations or in the poor phenotype definition. A genetic study was performed using a narrower phenotype of COPD. The authors studied 86 healthy smokers and 63 COPD subjects who were enrolled based on irreversible airflow obstruction (forced expiratory volume in one second/forced vital capacity <70% predicted) and a diffusing capacity for carbon monoxide <50% predicted (moderate-to-severe COPD associated with pulmonary emphysema). The following polymorphisms were investigated: TNF-308, the biallelic polymorphism located in the first intron of the lymphotoxin-alpha gene, and exon 1 and exon 6 of the TNF receptor 1 and 2 genes, respectively. No significant deviations were found concerning the four polymorphisms studied between the two populations. The authors confirm that the tumour necrosis factor family genes, at least for the polymorphisms investigated, are not major genetic risk factors for chronic obstructive pulmonary disease in Caucasians, either defined in terms of emphysema (this study) or airflow obstruction (previous studies). Nevertheless, the authors would like to emphasise the importance of narrowing the phenotype in the search for genetic risk factors in chronic obstructive pulmonary disease.
Pubmed
Journal: American journal of physiology. Regulatory, integrative and comparative physiology
March/30/2003
Abstract
Leptin deficiency in ob/ob mice increases susceptibility to endotoxic shock, whereas leptin pretreatment protects them against LPS-induced lethality. Lack of the long-form leptin receptor (Ob-Rb) in db/db mice causes resistance. We tested the effects of LPS in C57BL/6J db(3J)/db(3J) (BL/3J) mice, which express only the circulating leptin receptors, compared with C57BL/6J db/db (BL/6J) mice, which express all short-form and circulating isoforms of the leptin receptor. Intraperitoneal injections of LPS significantly decreased rectal temperature and increased leptin, corticosterone, and free TNF-alpha in fed and fasted BL/3J and BL/6J mice. TNF-alpha was increased three- and fourfold in BL/3J and BL/6J, respectively. LPS (100 microg) caused 50% mortality of fasted BL/6J mice but caused no mortality in fasted BL/3J mice. Pretreatment of fasted BL/3J mice with 30 microg leptin prevented the drop in rectal temperature, blunted the increase in corticosterone, but had no effect on TNF-alpha induced by 100 microg LPS. Taken together, these data provide evidence that fasted BL/3J mice are more resistant than BL/6J mice to LPS toxicity, presumably due to the absence of leptin receptors in BL/3J mice. This resistance may be due to high levels of free leptin cross-reacting with other cytokine receptors.
Pubmed
Journal: Arthritis and rheumatism
July/30/2003
Abstract
OBJECTIVE
To test whether the G-to-A polymorphism at position -308 in the promoter of the tumor necrosis factor alpha (TNFalpha) gene influences response to infliximab therapy in patients with rheumatoid arthritis (RA).
METHODS
We genotyped 59 RA patients by polymerase chain reaction and subdivided them into two groups: those with the A/A or A/G genotype and those with the G/G genotype. We compared the groups' clinical responses to infliximab treatment after 22 weeks, using the Disease Activity Score in 28 joints (DAS28).
RESULTS
We found that 42% of patients in the A/A and A/G group and 81% of patients in the G/G group had improvement of at least 1.2 in the DAS28 score (P = 0.0086). The average improvement in the DAS28 score was 1.24 in the A/A and A/G patients and 2.29 in the G/G patients (P = 0.029).
CONCLUSIONS
These data suggest that patients with a TNFalpha -308G/G genotype are better infliximab responders than are patients with A/A or A/G genotypes. TNFalpha -308 genotyping may be a useful tool for predicting response to infliximab treatment.
Pubmed
Journal: Experimental oncology
January/8/2017
Abstract
BACKGROUND
Cervical carcinoma cells including those infected with the oncogenic human papilloma virus (HPV) and several cervical carcinoma cell lines show a strong expression of the CD40 receptor, unlike benign cervical epithelial cells infected with HPV. The functional relevance of this up-regulated expression in the tumor is not fully understood. Nevertheless, it might offer a unique possibility to target those malignant cells due to the antiviral and antitumoral effects of the CD40/CD40 ligand (CD40L) interactions.
OBJECTIVE
In vitro assessment of the effect of CD40L on HPV 18-P105 promoter activity and the subsequent release of IL-6 by the promoter transfected HeLa(CD40) cells, which express CD40 constitutively.
METHODS
Transfection of HeLa(CD40) cells was achieved by electroporation after optimizing the parameters by the pCMV-β-Gal vector and β-Gal stain. Transfected HeLa(CD40) cells were challenged with BHK(CD40L) and TNFα, in addition to BHK(wt) and medium alone as controls. HPV18-P105 promoter activity was demonstrated by luciferase reporter gene assay while IL-6 was assessed by ELISA.
RESULTS
CD40/CD40L interactions and TNFα treatment significantly reduced HPV18-P105 promoter activity (56.0 ± 10.2% and 64.1 ± 9.1% vs. control, respectively; p < 0.001). Likewise, IL-6, which is a sensitive cytokine of CD40 activation, was significantly increased in HeLa(CD40) cells in the same experiments (2.7 fold after stimulation with BHK(CD40L) and 5.2 fold after stimulation with TNFα vs. control; p < 0.01 and p < 0.001, respectively).
CONCLUSIONS
It is likely that the CD40/CD40L interactions and TNFα are effective against cervical carcinomas by repressing transcriptional activity of HPV promoter. This can result in new adjuvant treatments.
Pubmed
Journal: Journal of animal science
October/20/1997
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