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

CD11c+ and CD11c- (CD123+) dendritic cells (DCs) have been described in blood. Both cell types express high levels of HLA-DR and lack the lineage markers CD3, CD14, CD19, CD20, CD16, and CD56. These immunophenotypic properties were used along with analysis of activation-related surface antigens and intracellular staining of cytokines to characterize functional responses of these DC subsets to stimuli in whole human blood (WB). Samples from healthy donors were activated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate plus ionomycin (PMA+I). The only distinct response in CD11c- DCs was the expression of CD25 upon PMA+I activation. CD11c+ cells responded to LPS stimulation by producing high levels of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), and lower levels of IL-6, IL-1Ra, and IL-8 and an increased expression of accessory molecules (CD25, CD40, CD80, CD86, HLA-DR, and HLA-DQ). PMA+I activation of CD11c+ cells resulted in high levels of IL-1beta and lower levels of IL-8, IL-1Ra, and TNF-alpha and up-regulation of CD80, CD86, HLA-DR, and HLA-DQ. Our data support prior observations of functional differences between peripheral blood DC subsets and demonstrate the power of multiparameter flow cytometry to characterize the pleiotropic responses of these cells to various stimuli.
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PMID:A flow cytometric immune function assay for human peripheral blood dendritic cells. 1077 Feb 87

Both genetic predisposition and environmental factors participate in the etiology of Type-1 diabetes. To test the role of the microbial product lipopolysaccharide (LPS) as an environmental trigger of autoimmune diabetes, we employed transgenic (tg) BDC2.5/NOD mice that bear an islet-specific CD4(+) T cell repertoire (>95%), but do not develop the spontaneous diabetes that typifies the NOD (nonobese diabetic) strain. LPS administration provoked diabetes in BDC2.5/NOD mice by their 16th week of age. However, LPS administration in NOD mice did not accelerate their diabetes. This finding indicates that the frequency of islet-specific T cells influences LPS-mediated diabetes. Furthermore, in vitro LPS-cultured splenocytes from BDC2. 5/NOD and BDC2.5-microMT (B-cell-deficient) mice effectively transferred diabetes into immunodeficient NOD-scid/scid mice but not immunosufficient NOD mice. Therefore, B lymphocytes are not required for LPS-provoked autoimmune diabetes. Flow cytometric analysis then revealed that LPS-stimulation in vitro induced the expression of an IL-2 receptor (CD25) on CD4 T cells; this indicates that the activation of islet-specific T cells is a prerequisite to eliciting diabetes in this situation. Overall, these results point to microbial LPS as an etiopathogenic agent of autoimmune diabetes.
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PMID:The microbial product lipopolysaccharide confers diabetogenic potential on the T cell repertoire of BDC2.5/NOD mice: implications for the etiology of autoimmune diabetes. 1077 2

CD7 and CD28 are Ig superfamily molecules expressed on thymocytes and mature T cells that share common signaling 0mechanisms and are co-mitogens for T cell activation. CD7-deficient mice are resistant to lipopolysaccharide (LPS)-induced shock syndrome, and have diminished in vivo LPS-triggered IFN-gamma and tumor necrosis factor (TNF)-alpha production. CD28-deficient mice have decreased serum Ig levels, defective IgG isotype switching, decreased T cell IL-2 production and are resistant to Staphylococcus aureus enterotoxin-induced shock. To determine synergistic roles CD7 and CD28 might play in thymocyte development and function, we have generated and characterized CD7/CD28 double-deficient mice. CD7/CD28-deficient mice were healthy, reproduced normally, had normal numbers of thymocyte subsets and had normal thymus histology. Anti-CD3 mAb induced similar levels of apoptosis in CD7-deficient, CD28-deficient and CD7/CD28 double-deficient thymocytes as in control C57BL/6 mice (P = NS). Similarly, thymocyte viability, apoptosis and necrosis following ionomycin or dexamethasone treatment were the same in control, CD7-deficient, CD28-deficient and CD7/CD28-deficient mice. CD28-deficient and CD7/CD28-deficient thymocytes had decreased [3H]thymidine incorporation responses to concanavalin A (Con A) stimulation compared to control mice (P < or = 0.01 and P < or = 0.05 respectively). CD7/CD28 double-deficient mice had significantly reduced numbers of B7-1/B7-2 double-positive cells compared to freshly isolated wild-type, CD7-deficient and CD28-deficient thymocytes. Con A-stimulated CD4/CD8 double-negative (DN) thymocytes from CD7/CD28 double-deficient mice expressed significantly lower levels of CD25 when compared to CD4/CD8 DN thymocytes from wild-type, CD7-deficient and CD28-deficient mice (P < 0.05). Anti-CD3-triggered CD7/CD28-deficient thymocytes also had decreased IFN-gamma and TNF-alpha production compared to C57BL/6 control, CD7-deficient and CD28-deficient mice (P < or = 0.05). Thus, CD7 and CD28 deficiencies combined to produce abnormalities in the absolute number of B7-1/B7-2-expressing cells in the thymus, thymocyte IL-2 receptor expression and CD3-triggered cytokine production.
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PMID:Comparison of thymocyte development and cytokine production in CD7-deficient, CD28-deficient and CD7/CD28 double-deficient mice. 1115 49

Type 1 diabetes is a chronic progressive autoimmune disease characterized by mononuclear cell infiltration, dominated by interleukin-12 (IL-12)-dependent Th1 cells, of the pancreatic islets, with subsequent destruction of insulin-producing beta-cells. Here, we demonstrate that treatment of adult nonobese diabetic (NOD) mice with an analog of 1alpha,25-dihydroxyvitamin D(3), an immunomodulatory agent preventing dendritic cell maturation, decreases lipopolysaccharide-induced IL-12 and gamma-interferon production, arrests Th1 cell infiltration and progression of insulitis, and inhibits diabetes development at nonhypercalcemic doses. Arrest of disease progression is accompanied by an enhanced frequency in the pancreatic lymph nodes of CD4(+)CD25(+) regulatory T-cells that are able to inhibit the T-cell response to the pancreatic autoantigen insulinoma-associated protein 2 and to significantly delay disease transfer by pathogenic CD4(+)CD25(-) cells. Thus, a short treatment of adult NOD mice with an analog of 1,25-dihydroxyvitamin D(3) inhibits IL-12 production, blocks pancreatic infiltration of Th1 cells, enhances CD4(+)CD25(+) regulatory cells, and arrests the progression of type 1 diabetes, suggesting its possible application in the treatment of human autoimmune diabetes.
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PMID:A 1alpha,25-dihydroxyvitamin D(3) analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. 1197 32

Capsiate and its dihydroderivatives are the major capsaicinoids of sweet pepper. These new capsaicinoids do not activate the vanilloid receptor type 1 (VR1) but they share with capsaicin (CPS)some biological activities mediated in a VR1-independent fashion. In this study we show that CPS and nordihydrocapsiate (CPT) inhibit early and late events in T cell activation, including CD69, CD25 and ICAM-1 cell surface expression, progression to the S phase of the cell cycle and proliferation in response to TCR and CD28 co-engagement. Moreover, both CPS and CPT inhibit NF-kappaB activation in response to different agents including TNF-alpha. CPS itself does not affect the DNA-binding ability of NF-kappaB but it prevents IkappaB kinase activation and IkappaBalpha degradation in a dose-dependent manner, without inhibiting the activation of the mitogen-activated protein kinases, p38, extracellular regulated kinase and c-Jun N-terminal protein kinase. Moreover, intraperitoneal pretreatment with CPT prevented mice from lethal septic shock induced by lipopolysaccharide. In a second model of inflammation CPT pretreatment greatly reduced the extensive damage in the glandular epithelium observed in the bowel of DSS-treated mice. Taken together, these results suggest that CPT and related synthetic analogues target specific pathways involved in inflammation, and hold considerable potential for dietary health benefits as well as for pharmaceutical development.
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PMID:Immunosuppressive activity of capsaicinoids: capsiate derived from sweet peppers inhibits NF-kappaB activation and is a potent antiinflammatory compound in vivo. 1211 59

A novel red pigment, 2,2'-[3-methoxy-1'amyl-5'-methyl-4-(1-pyrryl)] dipyrryl-methene (MAMPDM), which has properties similar to those of prodigiosins, has been isolated for the first time from a bacterium putatively identified as Micrococcus sp. Our studies showed that MAMPDM inhibited proliferation of both human T as well as B cells and murine T cells, in response to polyclonal mitogens, in a concentration-dependent manner while murine B cell proliferation induced by lipopolysaccharide was inhibited only at high concentration. The effect of MAMPDM on constitutive cell cycling was ascertained using four mouse and human tumour cell lines. At 100 nM, the concentration that inhibited con A induced proliferation of mouse spleen cells, the viability of these cell lines was not affected. At 10-100-fold higher concentration of MAMPDM, however, there was a decrease in cell viability with T cell-derived cell lines being more sensitive. MAMPDM did not block the secretion of IL-2 or expression of CD25 though it inhibited the proliferation of con A stimulated T cells. The higher amount of IL-2 in the supernatant of the con A stimulated T cells, cultured in the presence of the immunomodulator, indicated accumulation of IL-2 due to its reduced utilisation. At inhibitory concentration, MAMPDM induced apoptosis in con A stimulated cells. Thus, MAMPDM may have considerable and selective T cell immunosuppressive potential and appears to act by a mechanism distinct from that of other known immunosuppressors.
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PMID:A novel prodigiosin-like immunosuppressant from an alkalophilic Micrococcus sp. 1258 97

Regulatory CD4 T cells (Treg) control inflammatory reactions to commensal bacteria and opportunist pathogens. Activation of Treg functions during these processes might be mediated by host-derived proinflammatory molecules or directly by bacterial products. We tested the hypothesis that engagement of germline-encoded receptors expressed by Treg participate in the triggering of their function. We report that the subset of CD4 cells known to exert regulatory functions in vivo (CD45RB(low) CD25(+)) selectively express Toll-like receptors (TLR)-4, -5, -7, and -8. Exposure of CD4(+) CD25(+) cells to the TLR-4 ligand lipopolysaccharide (LPS) induces up-regulation of several activation markers and enhances their survival/proliferation. This proliferative response does not require antigen-presenting cells and is augmented by T cell receptor triggering and interleukin 2 stimulation. Most importantly, LPS treatment increases CD4(+) CD25(+) cell suppressor efficiency by 10-fold and reveals suppressive activity in the CD4(+) CD45RB(low) CD25(-) subset that when tested ex-vivo, scores negative. Moreover, LPS-activated Treg efficiently control naive CD4 T cell-dependent wasting disease. These findings provide the first evidence that Treg respond directly to proinflammatory bacterial products, a mechanism that likely contributes to the control of inflammatory responses.
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PMID:Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. 1259 98

It has been reported that bacterial superantigens induce interleukin (IL)-12 dependent expression of the cutaneous lymphocyte associated antigen (CLA) and that this may be relevant to the association between certain skin diseases and infections including psoriasis and streptococcal tonsillitis. We have confirmed that the streptococcal pyrogenic superantigen C (SpeC) increases CLA expression by both CD4+ and CD8+ T cells when PBMCs are incubated in medium enriched with fetal calf serum (FCS). However, such an increase could not be induced in medium enriched with human serum (HS) even when recombinant IL-12 was added to the PBMCs cultures. Strikingly, CD4+ T cells incubated with SpeC in HS showed a marked reduction in CLA expression, which was not due to apoptosis. In contrast, SpeC did induce T cell proliferation and expression of CD25, CD54 and CD103 in the presence of HS indicating that the absence of SpeC induced CLA expression in HS was not due to SpeC inhibitors. Although addition of low amounts of lipopolysaccharide endotoxin (LPS) caused a highly significant increase in CLA expression in the absence of SpeC in cultures enriched with HS, a combination of LPS and SpeC did not increase CLA expression beyond that induced by LPS alone. The superantigen-induced CLA expression in FCS was partially inhibited by anti-IL-12 but not by anti-IL-18 or antibodies to transforming growth factor (TGF)-beta. It is concluded that IL-12 alone can not increase CLA expression but requires the help of other factor(s) present in FCS but not in HS. Although LPS can induce CLA expression it does not seem to be the factor that interacts with IL-12 to induce superantigen-mediated CLA expression in cultures enriched with FCS.
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PMID:Interleukin-12 alone can not enhance the expression of the cutaneous lymphocyte associated antigen (CLA) by superantigen-stimulated T lymphocytes. 1278 Jun 89

Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II-restricted interferon gamma-producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.
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PMID:CD4+ CD25+ regulatory T cells control T helper cell type 1 responses to foreign antigens induced by mature dendritic cells in vivo. 1287 59

The immunomodulatory activity of a standardized water soluble fraction of the fern Phlebodium decumanum (EXPLY-37) previously shown to have "in vivo" anti-inflammatory activity was analyzed "in vitro". This extract inhibited tumor necrosis factor (TNF) production by macrophages activated with lipopolysaccharide (LPS) or LPS plus interferon (IFN)-gamma. In contrast, nitric oxide (NO) and interleukin (IL)-1beta production were not affected in the same cultures, whereas IL-6 production was partially inhibited. More interestingly, EXPLY-37 increased the release of soluble TNF-receptor 2 (sTNFR2) and of IL-1R antagonist (IL-1Ra) but not of sTNFR1, by activated macrophages. EXPLY-37 had no effect on T lymphocyte activation, measured as proliferation as well as expression of early and late cell surface antigens CD69, CD25 (IL-2R-alpha) and CD71 (transferrin receptor) at the cell membrane. At the molecular level, EXPLY-37 did not inhibit the activation of the nuclear factor kappa B (NF-kappaB) transcription factor by TNF. In summary, EXPLY-37 has two anti-inflammatory activities "in vitro": it decreases TNF production and increases IL-1Ra and sTNFR2, which may be able to neutralize IL-1 and TNF activity, respectively.
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PMID:In vitro anti-inflammatory activity of Phlebodium decumanum. Modulation of tumor necrosis factor and soluble TNF receptors. 1289 Apr 27


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