Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocytes play a pivotal role in various human infectious and inflammatory diseases. To reveal a whole picture of pathophysiologic function of activated human monocytes, this study used the serial analysis of gene expression (SAGE) procedure in lipopolysaccharide (LPS)-stimulated human monocytes. A total of 35 874 tags corresponding to more than 12 000 different transcripts were sequenced. Comparison of gene expression profile with that of resting monocytes revealed the LPS-inducible gene expression profile. Many cytokines and chemokines, including interleukin (IL)-6, IL-1alpha, IL-1beta, tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1beta, MIP-2beta, MIP-2alpha, liver and activation-regulated chemokine (LARC), MIP-1alpha, thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), growth-regulated oncogene (GRO) alpha, and IL-8, were observed in the highest inducible transcripts. Other genes encoding plasminogen activator inhibitor type 2 (PAI-2), Hc-gp39, apolipoproteins, malate dehydrogenase, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase (COX2) were also highly elevated in LPS-stimulated monocytes. Moreover, up-regulation of Naf1beta, IL-7 receptor, adenosine receptor A2a, and many novel genes was newly identified. These results suggest that the LPS-inducible gene products may be involved in cell activation and migration, angiogenesis, tissue remodeling, and metabolism, and thus may orchestrate the inflammatory reactions. On the other hand, the expression of numerous sets of novel genes was discovered to be down-regulated on LPS stimulation. This study represents the first comprehensive analysis of LPS-inducible gene expression in human monocytes and provides tremendous novel information for the function of LPS-activated monocytes and targets for diagnosing, monitoring, and treating sepsis and various human infectious and inflammatory diseases.
 ...
PMID:Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE. 1100 15

Premature delivery results from multiple closely interdependent factors. Inflammation is most generally caused by cervicovaginal infection that may progress to intra-uterine infection or inflammation. Severe chorioamniotitis is found in 75% of all premature deliveries compared with 15% in term deliveries. Premature rupture of the membranes is the cause of premature delivery in 30-40% of premature deliveries although the diagnosis of chorioamniotitis can also be established with intact membranes, sometimes on the basis of histological findings alone. The degree of prematurity is correlated with the severity of the histological chorioamniotitis. The severity and the duration of the lesions is often the cause of antibiotic failure for the treatment of threatening premature delivery. Inflammation mediators, mainly proinflammatory cytokines (IL1, TNF-alpha), chemokines (IL6, IL8 and MIP-1alpha) and immunomodulator cytokines (IL6) and immunosuppressive cytokines (IL10, IL4) are produced by the amniotic and decidual membranes and are found in the fetal circulation and amniotic fluid. This reaction triggers a cascade of events leading to the production of prostaglandins and cyclooxygenase (COX2) activity, that cause uterine contractions. The inflammation may be initiated locally, even from an extrapelvic location, This leads to a fetal and/or maternal systemic inflammatory reaction. Systemic fetal expression of deregulated inflammatory phenomena can lead to neonatal lesions of lung and brain white matter tissue. This explains the failure of tocolysis and antibiotics in uncontrolled situations and suggests new avenues for therapy using selective inhibitors of COX2.
 ...
PMID:[Premature delivery and inflammation]. 1124 May 12

This paper lists the genotype frequencies of 50 polymorphisms of 37 genes (ALDH2, ADRB2, ADRB3, COMT, CD36, CXCR2, CCND1, COX2, CYP2A6, CYP17, CYP19, IGF1, IL-1A, IL-1B, IL-1RN, IL-1R1, IL-6, IL-8, IL-10, LEP, Le, L-myc, MPO, MTR, MTHFR, MAO-A, NQO1, OGG1, p53, p73, Se, SRD5A2, TGF-B, TNF-A, TNF-B, XPD, and XRCC1) and 6 sets of combined genotype frequencies for 241 non-cancer Japanese outpatients. Though the genotype frequencies of 25 polymorphisms have already been reported in our previous papers, 15 polymorphisms (CD36 A52C, CXCR2 C785T, CCND1 G870A, IGF1 C/T at intron 2 and G2502T, IL-1A 46-bp VNTR, IL-1R1 C-116T, IL-6 Ins/Del 17C, IL-8 A-278T and C74T, IL- 10 T-819C, LEP A-2548G, SRD5A2 2-bp VNTR, XPD Lys751Gln, and XRCC1 Arg399Gln) and six sets of combined genotype frequencies (IL-1B C-31T and IL-1A C-889T, IL-1B C-31T and IL-1RN 86-bp VNTR, IL-1B C-31T and IL-1R1 C-116T, TNF-A G-308A and TNF-B A252G, SRD5A2 Val89Leu and 2-bp VNTR, and XRCC1 Arg399Gln and XPD Lys751Gln) were reported in this paper for the first time for Japanese. Although microarray technology will produce this kind of information in near future, this is the first document that reports the genotype/allele frequencies among Japanese for an archival purpose.
 ...
PMID:Genotype frequencies of 50 polymorphisms for 241 Japanese non-cancer patients. 1216 25

Tumor necrosis factor (TNF) is a key mediator in regulating the inflammatory response. Previously two TNF genes have been cloned and sequenced from rainbow trout, Oncorhynchus mykiss. In this study, the mature peptides of the two TNF molecules were produced in bacteria, purified under native conditions and their bioactivities evaluated in vitro. Both trout rTNF1 and rTNF2 induced gene expression of a number of proinflammatory factors including IL1beta, TNF1, TNF2, IL8 and COX2 in freshly isolated head kidney leucocytes and the macrophage cell line RTS11. The stimulatory doses of both rTNFs were >or=10 ng/ml. Moreover, leucocyte migration and phagocytic activity were enhanced in vitro by the rTNFs in a dose dependent manner. Western blot analysis revealed the presence of multiple forms of rTNF structures including monomeric, dimeric and trimeric forms, suggesting that formation of a homotrimeric structure may be essential for the TNF bioactivities.
 ...
PMID:Functional characterisation of the recombinant tumor necrosis factors in rainbow trout, Oncorhynchus mykiss. 1281 38

The metabolism of arachidonic acid through the cyclooxygenase pathway is a highly regulated cellular process that results in the formation of PGH2. This unstable intermediate can be enzymatically metabolized to PGE2 by the actions of a microsomal 17 kDa PGE synthase (mPGES1). Treatment of A549 cells with IL-1beta for 24 h resulted in a twofold increase in mPGES1 mRNA, protein expression, and PGES specific activity. To understand the relationship between expression of mPGES1 and PGE2 formation, IL-1beta treated cells were incubated with increasing concentrations of antisense oligonucleotides (ASO) and their effects compared to cells treated with reverse sense oligonucleotides (RSO) designed against the ATG translation initiation codon of mPGES1. Incubation with ASO resulted in a 44% reduction in mRNA expression level as compared to RSO-treated cells. Microsomal preparations isolated from ASO- and RSO-treated cells were analyzed for their ability to convert PGH2 to PGE2 in the presence 2.5 mM reduced glutathione. An approximate 50% reduction (ASO: 1.8 nmol/min/mg, RSO: 3.7 nmol/min/mg) in PGES activity, protein expression by immunodetection, and extracellular PGE2 release was detected in these samples. As a control in these studies, the protein levels of COX2 and secreted IL-8 were quantified; no change in these levels was observed. These results demonstrate the direct association between mPGES1 expression, its enzymatic activity, and total PGE2 production following an inflammatory stimulus.
 ...
PMID:Inhibition of IL-1beta-dependent prostaglandin E2 release by antisense microsomal prostaglandin E synthase 1 oligonucleotides in A549 cells. 1289 May 77

Rheumatoid arthritis is characterised by the interaction of multiple mediators, among the most important of which are cytokines. In recent years, extensive data demonstrates a pivotal role for one cytokine, macrophage migration inhibitory factor (MIF), in fundamental events in innate and adaptive immunity. MIF has now been demonstrated to be involved in the pathogenesis of many diseases, but in the case of RA the evidence for a role of MIF is very strong. MIF is abundantly expressed in the serum of RA patients, and in RA synovial tissue where it correlates with disease activity. MIF induces synoviocyte expression of key proinflammatory genes including TNF, IL-1, IL-6, IL-8, cPLA2, COX2 and MMPs. MIF also regulates the function of endothelial cells and B cells. Moreover, MIF is implicated in the control of synoviocyte proliferation and apoptosis via direct effects on the expression of the tumor suppressor protein p53. In multiple rat and mouse models of RA, anti-MIF antibodies or genetic MIF deficiency are associated with significant inhibition of disease. MIF -/- mice further demonstrate increases in synovial apoptosis. That the human Mif gene is encoded by different functional alleles in subjects with inflammatory disease also provides evidence for the role of MIF in RA. The mechanism of action of MIF is becoming better understood. MIF appears to interact with cell surface CD74, with consequent activation of MAP kinases but possibly not NFkappaB intracellular signal transduction. This apparent selectivity may be implicated in the ability of MIF to antagonise the effects of glucocorticoids. As MIF expression is induced by glucocorticoids, inhibition of its antagonistic effects may permit enhanced therapeutic effect of glucocorticoids, or "steroid sparing". To date there are no clinical trials of MIF antagonism in any disease, but exploitation of antibody, soluble receptor, or small molecule approaches enabled by the unique crystal structure of MIF, may soon lead to the ability to test in the clinic the importance of this cytokine in human RA.
 ...
PMID:Macrophage migration inhibitory factor in rheumatoid arthritis. 1557 36

Use of non-steroid anti-inflammatory drugs (NSAIDs) has been associated with decreased risk of breast cancer in epidemiological studies. Thus, a high-inflammatory response may be associated with increased breast cancer risk. It is thus possible that genetic variations leading to a modified inflammatory response will influence breast cancer risk. The purpose of this study was to determine if polymorphisms associated with an altered inflammatory response are associated with breast cancer risk, and to investigate the possible interaction with lifestyle factors such as alcohol use, smoking and NSAID use. We matched 361 female breast cancer cases with 361 controls, nested within the prospective 'Diet, Cancer and Health' study. Carriers of the variant Ala-allele of PPARgamma2 Pro12Ala were at lower risk of breast cancer (IRR=0.67, 95% CI=0.46-0.97). This was primarily due to an interaction with alcohol consumption. Alcohol consumption was associated with a 1.21-fold increased risk of breast cancer per 10 g alcohol/day (95% CI=1.06-1.35) among homozygous wild-type carriers, whereas alcohol was not associated with breast cancer risk among variant allele carriers (P for interaction=0.005). Non-users of NSAID, who were carriers of the variant allele of PPARgamma2 Pro12Ala, were at lower risk of breast cancer (IRR=0.44; 95% CI=0.26-0.73) compared with non-users carrying wild-type alleles (P for interaction=0.03). No effects were found for IL6 G-174C, IL8 T-251A and COX2 T8473C. Our results suggest that PPARgamma2 Pro12Ala is an important determinant in alcohol mediated breast carcinogenesis. We also observe interaction between NSAID, alcohol consumption and PPARgamma2 Pro12Ala genotype in relation to breast cancer risk.
 ...
PMID:Peroxisome proliferator-activated [corrected] receptor-gamma2 [corrected] Pro12Ala, interaction with alcohol intake and NSAID use, in relation to risk of breast cancer in a prospective study of Danes. 1695 87

Lung cancer risk was investigated in relation to single nucleotide polymorphisms in genes involved in the inflammatory response. The aim was to see if polymorphisms modifying the inflammatory response are associated with risk of lung cancer and if there were interactions between the same polymorphism and factors, which modify an inflammatory response, such as smoking status, duration, and intensity, and use of NSAID. The functional SNPs IL-1B T-31C, IL6 G-174C, IL8 T-251A, IL10 C-592T, COX2 C8473T, COX2 A-1195G and PPARgamma2 Pro(12)Ala were included. A case-cohort study including 428 lung cancer cases and a sub-cohort of 800 persons was nested within a population-based prospective study of 57,053 individuals. Variant allele carriers of IL-1B T-31C were at increased risk of lung cancer (IRR=1.51, 95% CI=1.08-2.12). There was interaction between the polymorphism COX-2 T8473C and smoking status. Thus, non-smoking variant allele carriers were at 5.75-fold (95% CI=1.25-26.43) higher risk of lung cancer than for homozygous wild type allele carriers. Lung cancer risk was similar for all genotype carriers among past and current smokers. There were, however, very few non-smoking lung cancer cases. There was interaction between IL-1B T-31C, COX-2 A-1195G and PPARgamma2 Pro(12)Ala and NSAID use in relation to lung cancer risk. For the two latter, NSAID use was only associated with a lower cancer risk among homozygous wild type allele carriers. p for interaction was 3 x 10(-6) for COX-2 A-1195G and 9 x 10(-5) for PPARgamma2 Pro(12)Ala. The results suggest that NSAID use may modify risk of lung cancer differently depending on the genotype.
 ...
PMID:Polymorphisms in genes involved in the inflammatory response and interaction with NSAID use or smoking in relation to lung cancer risk in a prospective study. 1816 40

UVR is an important environmental carcinogen and a powerful modulator of the cutaneous immune system. Exposure to UVR activates many signaling pathways leading to changes in the expression of several hundred genes. While the covalent modification of histones has been shown to play a central role in regulating gene expression, the impact of UVR on histone modifications and the contribution of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to the UVR-induced transcriptional response have not been completely characterized. In this report, we have examined the impact of UVR on histone H3 K9/14 acetylation. The potential role of UVR-induced histone acetylation in the UVR transcriptional response was also explored using the HAT inhibitor curcumin and HDAC inhibitor trichostatin A (TSA). We found that UVR caused an increase in histone H3 acetylation within the promoter regions of ATF3, COX2, IL-8, MKP1 and MnSOD. In most of the regions examined, histone H3 acetylation peaked 24 h after UVR and then returned to baseline levels by 72 h. The induction of ATF3, COX2 and MKP1 was blocked in the presence of curcumin at doses that decrease in vivo histone H3 acetylation but not at lower doses that do not affect acetylation levels. We also provide evidence that for ATF3, a transcriptional superinduction occurs after repeat exposures to UVR that can be recapitulated when the second UVR exposure is replaced with TSA treatment. Thus, UVR can alter histone acetylation within human keratinocytes and these changes may contribute to the UVR-transcriptional response.
 ...
PMID:Ultraviolet radiation-induced transcription is associated with gene-specific histone acetylation. 1907 6

Aberrant local inflammatory signaling within skeletal muscle is now considered a contributing factor to the development of sarcopenia. Recent evidence indicates that chronic resistance training contributes to the control of locally derived inflammation via adaptations to repeated, acute increases in pro-inflammatory mRNA within muscle. However, only a limited number of gene transcripts related to the inflammatory process have been examined in the literature. The present study utilized an acute bout to examine the effects of resistance exercise on several inflammatory-related genes in 24 physically active, post-menopausal women not currently undergoing hormone replacement therapy. Following a standard warm-up, participants completed a lower-body resistance exercise bout consisting of 3 sets of 10 repetitions on machine squat, leg press, and leg extension exercises (80% intensity). Muscle biopsies were obtained from the vastus lateralis of the dominant leg at baseline and 3 h following exercise. Significant (p < 0.05) up-regulation in mRNA content was observed for TNFalpha, IL1beta, IL6, IL8, SOCS2, COX2, SAA1, SAA2, IKKB, cfos, and junB. Muscle mRNA content was not significantly altered at the 0.05 level for IL2, IL5, IL10, or IL12 (p35). Venous blood samples were also obtained at baseline as well as at 3, 24, and 48 h post-exercise. Serum was analyzed for circulating TNFalpha, IL1beta, IL6, IL8, COX2, and SAA with no significant changes observed. These results indicate that resistance exercise is capable of up-regulating transcription of numerous inflammatory mediators within skeletal muscle, and these appear to be worthy of future examination in chronic studies.
 ...
PMID:Resistance exercise-induced changes of inflammatory gene expression within human skeletal muscle. 1966 88


1 2 3 4 5 6 Next >>