Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin (IL)-12 is an inducer of differentiation of T helper (Th) cells towards Th1, whereas IL-10 is mainly an anti-inflammatory cytokine inhibiting Th1 functions. Single nucleotide polymorphisms (SNPs) in the regulatory sequences of genes are presumed to be associated with the differential production of cytokines. One IL12B 3'untranslated region (UTR) and five of IL10 gene promoter region SNPs were screened in 152 individuals by genotyping. IL-10 and IL-12 secretion of lipopolysaccharide (LPS), purified protein derivative (PPD) and Staphylococcus aureus Cowan strain I (SAC) stimulated peripheral blood mononuclear cells (PBMCs) was determined. The frequencies of the less frequent IL12B +16974 C, IL10 -2763 A -3575 A, -1082 G, -819 T and -592 A alleles were 27.4, 32.2, 25.9, 14.8, 9.3 and 8.6%, respectively. Individuals CC homozygous at IL12B 3'UTR had significantly higher IL-12 secretion levels from LPS and PPD stimulated PBMCs than AC heterozygotes (P = 0.03 and P = 0.02) or AA homozygotes (P = 0.02 and P = 0.05, respectively). IL10 -2763 and -3575 SNPs did not show any effect on in vitro secretion levels, whereas the association of proximal promoter -1082 SNP with IL-10 production is confirmed. IL10 proximal and distal promoter SNP distribution with estimated haplotype variations has implicated considerable similarities with the Caucasian populations in Turkey.
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PMID:IL-12 and IL-10 polymorphisms and their effects on cytokine production. 1586 93

Infection with influenza virus strongly predisposes an individual to bacterial superinfection, which is often the significant cause of morbidity and mortality during influenza epidemics. Little is known about the immunomodulating properties of the virus that lead to this phenomenon, but the effect of the viral components on the development of immune dendritic cells (DCs) may prove vital. In this study, activation of and cytokine secretion by bacterial lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) following treatment with the influenza virus major antigen haemagglutinin (HA) were examined. HA selectively inhibits the release of LPS-induced interleukin 12 (IL12) p70, which is independent of IL10 secretion. Suppression occurs at the transcriptional level, with selective inhibition of p35- and not p40-subunit mRNA expression. The downregulation of IL12 p70 by influenza HA is a novel and unexplored pathway that may be relevant in the predisposition to bacterial superinfection associated with influenza virus infections.
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PMID:Novel mechanism of immunosuppression by influenza virus haemagglutinin: selective suppression of interleukin 12 p35 transcription in murine bone marrow-derived dendritic cells. 1595 66

Toll-like receptor 4 (TLR4) induces an innate immune response in mammals by recognizing lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria. In this study, we show that tyrosine kinase Syk constitutively associates with TLR4 in THP-1 cells. As previously reported in peripheral blood mononuclear cells, TLR4 gets inducibly tyrosine phosphorylated upon LPS engagement in THP-1 cells. Piceatannol, a pharmacological inhibitor of the tyrosine kinase Syk, abrogates TLR4 tyrosine phosphorylation at low doses. The kinetics of TLR4 tyrosine phosphorylation in THP-1 cells coincides with an early wave of Syk tyrosine phosphorylation. Additionally, serine threonine kinase interleukin-1 (IL1) receptor-associated kinase 1 (IRAK-1) is transiently recruited to the complex containing adaptor molecule MyD88, TLR4 and Syk within 1 min of LPS engagement and dissociates by 30 min. Finally, the inhibition of Syk with piceatannol has no effect on LPS-mediated release of cytokines IL6, IL1beta, tumor necrosis factor-alpha, neither on chemokines macrophage inhibitory protein (MIP)1alpha, MIP1beta, monocyte chemoattractant protein -1, IL8, Groalpha and RANTES. However, IL10 and IL12p40 releases are significantly inhibited. Our findings implicate Syk as a novel modulator of LPS-mediated TLR4 responses in human monocytic cells and shed insight into the kinetics of early complex formation upon LPS engagement.
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PMID:Tyrosine kinase Syk associates with toll-like receptor 4 and regulates signaling in human monocytic cells. 1722 23

Two M5.1 and M15.2 B complex congenic lines of Fayoumi chickens were evaluated for body weight loss and faecal oocyst counts as parameters of avian coccidiosis. M5.1 chickens exhibited resistance to E. maxima compared with M15.2. To correlate the differential responses of the M5.1 and M15.2 lines to E. maxima infection with cellular immune responses, the expression levels of mRNAs encoding 14 immune-related molecules were measured by quantitative RT-PCR in intestinal intraepithelial lymphocytes (IELs) and splenocytes at 0, 3, 4, and 5 days following parasite infection. Intestinal IELs from M5.1 chickens expressed higher levels of transcripts encoding interferon gamma (IFNG), interleukin-lbeta (1L1B), IL6, IL8, IL12, IL15, IL17A, inducible nitric oxide synthase (iNOS), and lipopolysaccharide-induced tumour necrosis a factor (LITAF), and lower levels of mRNAs for IFNA, IL10, IL17D, NK-lysin (NKL), and tumour necrosis factor superfamily 15 (TNFSF15) at 3 days post infection, compared with the M15.2 line. In the spleen, E. maxima infection was associated with higher expression levels of IFNA, and IL15 and lower levels of IL6, IL17D, and IL12 in M5.1 compared to M15.2 birds. Using an intestinal IEL cDNA microarray, the differential dynamics of gene expression in the gut of M5.1 and M15.2 chickens following experimental coccidiosis were evident. In particular, the genes encoding lymphotactin and parathymosin were expressed at significantly higher levels in M5.1 compared with M15.2 line chickens. In conclusion, genetic determinants within the chicken major histocompatibility complex (MHC) B complex influence resistance to E. maxima infection by controlling the local and systemic expression of immune-related cytokine and chemokine genes.
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PMID:Differential immune-related gene expression in two genetically disparate chicken lines during infection by Eimeria maxima. 1881 95

IL-10 is an immunomodulatory cytokine that regulates inflammatory responses of mononuclear phagocytes (monocytes and macrophages). Mononuclear cells exposed to microbes or microbial products secrete a host of proinflammatory cytokines followed by delayed onset of anti-inflammatory IL-10. IL-10 suppresses immune responses by inhibiting cytokine production by mononuclear phagocytes. Using THP-1, a human promonocytic leukemia cell line, we show that endotoxin/lipopolysaccharide (LPS) exposure induces IL10 expression while IFN-gamma blocks this LPS-mediated effect. IFN-gamma is an important modulator of IL-10 production during infectious diseases. We show that LPS and IFN-gamma regulate IL10 expression in THP-1 cells in part through posttranscriptional mechanisms. Our results demonstrate that 3'-untranslated region (3'-UTR) AU-rich elements (AREs) decrease expression of a chimeric luciferase reporter gene in THP-1 cells. The ARE-binding protein AUF1 binds the IL10 3'-UTR. Depletion of AUF1 by RNAi suppresses LPS-mediated induction of IL10 mRNA and protein without affecting LPS-mediated stabilization of IL10 mRNA. Upon complementation with either RNAi-refractory p37 or p40 AUF1 plasmids, only p40 restores LPS-mediated induction of IL10 mRNA and protein to near normal levels. Thus, the p40 AUF1 isoform selectively plays a critical, positive role in IL10 expression upon LPS exposure.
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PMID:AUF1 isoform-specific regulation of anti-inflammatory IL10 expression in monocytes. 1884 78

Interleukin-10 is the most important anti-inflammatory cytokine that controls the progress of the immune response. The molecular mechanisms driving the IL10 gene regulation are not well understood. To gain insight into this process we studied the IL-10 expression on mRNA and protein levels, together with c-Jun, FOXP3 and RelA transcription factors gene expression in human monocytes. We investigated also, the involvement of JNK and p38 transduction pathways in IL-10, c-Jun, FOXP3 and RelA gene expression. The quantity determination of IL-10 was performed by ELISA. qRT-PCR was performed for the detection of mRNA transcripts. The pharmacological inhibitors SP600125 and SB202190 were used to explore JNK and p38 MAPKs involvement in IL10, c-Jun, FOXP3 and RelA gene expression. The measurement of IL-10 mRNA synthesis, triggered by lipopolysaccharide (LPS) or C3 binding glycoprotein (C3bgp) showed that stimulation with both inducers led to similar high level of IL-10 mRNA synthesis, whereas C3bgp was the stronger inducer of IL-10 production than LPS. JNK and p38 inhibition significantly decreased IL-10 expression in stimulated cells. C3bgp and LPS induced comparatively low expression of FOXP3, RelA and c-Jun mRNA in monocytes. The inhibition of p38 MAPK in stimulated monocytes resulted in significant enhancement of c-Jun mRNA synthesis suggesting the functional relation between p38 MAPK and c-Jun gene expression. We concluded that the IL10 gene transcription did not associate with enhancement of c-Jun, RelA and FOXP3 gene expression and strictly depended on the JNK and p38 MAPKs activation in stimulated human monocytes.
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PMID:The inhibition of JNK and p38 MAPKs downregulates IL-10 and differentially affects c-Jun gene expression in human monocytes. 1923 39

Cardiac surgery using cardiopulmonary bypass (CPB) causes a systemic inflammatory response. Additionally, an impairment of the responsiveness of peripheral blood mononuclear cells (PBMC) to further immunological stimuli has been observed. The aim of our present study was to evaluate the ability of antioxidant therapy with mannitol or haemofiltration during CPB to modulate this immunosuppression after CPB. Forty-five patients undergoing elective heart-surgery were prospectively enrolled and randomized into three groups (control, mannitol, haemofiltration). Blood samples were taken after induction of anaesthesia (T1), 20 min after CPB (T2) and 24 h post-operatively (T3). Expression density of the monocytic surface receptor CD14, HLA-DR expression and cytokine release (TNF-alpha and IL10) after lipopolysaccharide-stimulation were evaluated. At T2, the CD14(dim) cell population was maintained in both intervention groups while in the control group there was a decrease of this proinflammatory monocytic phenotype. No significant differences regarding HLA-DR expression or cytokine release could be demonstrated. This study shows that the suppression of the stimulated immune response after CPB can potentially be alleviated by mannitol or haemofiltration in an experimental in-vitro setting. In the light of data showing that this depression of the immune response might affect the post-operative course of patients, these results could have a potential clinical relevance.
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PMID:Effects of haemofiltration and mannitol treatment on cardiopulmonary-bypass induced immunosuppression. 1928 35

IL-10 production shows a broad-spectrum of individual response, suggesting a genetic component of approximately 75%. Different polymorphisms located close to, or within the IL-10 gene has been demonstrated to influence its transcription rate whereas the post-transcriptional regulation of IL-10 production has not well elucidated. The main responsible elements at this control level are both the 5'- and 3'-untranslated regions (UTR's) of mRNAs, and as the 3'-UTR regions are mainly involved in the stability and decay rate of mRNAs, the 5'-UTR regions mediate the binding rate of the molecule with ribosomal 40S subunit as a cis-acting element. Herein are report data on the identification of two IL10 mRNA that differ by the length of respective 5'UTR regions (160 and 288 nucleotides, respectively; EMBL accession nrs: EU751618 and EU751619) produced after stimulation of human blood samples with bacterial lipopolysaccharide (LPS). The longer 5'UTR is constitutively expressed in unstimulated PBMC cells cultured at 37 degrees C for 24h, while in LPS stimulated cells an additional IL-10 mRNA molecule, containing a shorter 5'UTR, is synthesized. RNADRAW software (http://www.rnadraw.com/) analysis have indicated that the secondary structures of the shorter 5'UTR IL-10 mRNA region is more available for the binding to the 40S ribosomal subunit. In conclusion, our data seem to suggest that LPS could influence the post-transcriptional control of IL-10 production inducing an alternative mRNA immediately available in response to the inflammatory stimulation.
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PMID:Characterization of two alternative Interleukin(IL)-10 5'UTR mRNA sequences, induced by lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells. 1947 25

Macrophages participate pivotally in the pathogenesis of many chronic inflammatory diseases including atherosclerosis. Adiponectin, a vasculoprotective molecule with insulin-sensitizing and anti-atherogenic properties, suppresses pro-inflammatory gene expression in macrophages by mechanisms that remain incompletely understood. This study investigated the effects of adiponectin on major pro-inflammatory signaling pathways in human macrophages. We demonstrate that pretreatment of these cells with adiponectin inhibits phosphorylation of nuclear factor kappaB inhibitor (IkappaB), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK), induced by either lipopolysaccharide (LPS) or tumor necrosis factor (TNF) alpha, as well as STAT3 phosphorylation induced by interleukin-6 (IL6). Antagonism of IL10 by either neutralizing antibodies or siRNA-mediated silencing did not abrogate the anti-inflammatory actions of adiponectin, indicating that the ability of adiponectin to render human macrophages tolerant to various pro-inflammatory stimuli does not require this cytokine. A systematic search for adiponectin-inducible genes with established anti-inflammatory properties revealed that adiponectin augmented the expression of A20, suppressor of cytokine signaling (SOCS) 3, B-cell CLL/lymphoma (BCL) 3, TNF receptor-associated factor (TRAF) 1, and TNFAIP3-interacting protein (TNIP) 3. These results suggest that adiponectin triggers a multifaceted response in human macrophages by inducing the expression of various anti-inflammatory proteins that act at different levels in concert to suppress macrophage activation.
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PMID:Adiponectin inhibits pro-inflammatory signaling in human macrophages independent of interleukin-10. 1961 29

The effects of different doses of tylosin on serum cytokine concentrations were investigated in healthy and lipopolysaccharide-treated mice. The mice were divided into seven groups. Lipopolysaccharide (LPS) was injected into the positive control group. The other six groups received three different tylosin doses concurrently without or with LPS: 10 mg/kg, 100 mg/kg, 500 mg/kg, 10 mg/kg + LPS, 100 mg/kg + LPS and 500 mg/kg + LPS. After treatment, serum samples were collected at 0, 1, 2, 3, 6, 12 and 24 hours. Serum tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta) and IL10 levels were determined by enzyme-linked immunosorbent assay (ELISA). Tylosin doses of 10 and 100 mg/kg induced no cytokine production in the healthy mice. Tylosin at 500 mg/kg had no effect on TNFalpha or IL1beta production, but it induced IL10 production in healthy mice. All doses of tylosin reduced the elevated TNFalpha and IL1beta in LPS-treated mice but increased their IL10 levels. In conclusion, these data suggest that tylosin has an immunomodulatory effect at the dose recommended for use against infection.
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PMID:Effects of tylosin on serum cytokine levels in healthy and lipopolysaccharide-treated mice. 2015 41


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