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)

We have examined the biological activity of the CC chemokine myeloid progenitor inhibitory factor 1 (MPIF-1) on human dendritic cells. MPIF-1 has chemotactic activity on dendritic cells derived from either peripheral blood monocytes or cord blood CD34+ progenitors. However, chemokine treatment did not induce further cell activation or maturation. In addition, MPIF-1 is constitutively released by monocyte-derived dendritic cells but not macrophages or monocytes (resting or stimulated). The proinflammatory stimuli lipopolysaccharide and tumor necrosis factor alpha, which induced the release of monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and interleukin-8, did not affect MPIF-1 release. In contrast, CD40 ligation and interferon-gamma treatment, while stimulating the production of the other chemokines, caused a pronounced reduction of MPIF-1 transcript and protein release. Thus, in dendritic cells the regulation of the production and release of MPIF-1 is distinct in comparison to other CC and CXC chemokines.
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PMID:Dendritic cells and MPIF-1: chemotactic activity and inhibition of endogenous chemokine production by IFN-gamma and CD40 ligation. 1038 Sep 5

Macrophage-derived cytokines and chemokines are involved at multiple steps of immune and inflammatory responses, and the transcriptional factor NF-kappaB appears to play a pivotal role in their coordinated upregulation. The anti-inflammatory agents salicylates have been proposed to act in part by inhibiting NF-kappaB. We have therefore studied the effects of sodium salicylate on lipopolysaccharide (LPS)-induced kappaB-binding activity and on cytokine and chemokine gene expression in the RAW264.7 murine macrophage cell line and compared them to those of an established NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). PDTC (100 microM) completely abrogated LPS-induced kappaB-binding activity and also profoundly inhibited the induction of interleukin 1alpha (IL-1alpha), IL-1beta, IL-6, IL-10, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and MCP-1 and, to a lesser extent, leukemia inhibitory factor, RANTES, and IL-1Ra. In contrast, sodium salicylate (15 to 20 mM) had no effect on NF-kappaB activation but, nevertheless, suppressed several LPS-induced cytokine and chemokine genes to a degree similar to that obtained with PDTC. However, compared to PDTC, sodium salicylate caused significantly less inhibition of IL-1Ra and IL-10 gene expression after LPS stimulation. Neither LPS-induced MIP-1alpha, MIP-1beta, nor MIP-2 was significantly affected by PDTC or sodium salicylate, demonstrating that NF-kappaB is dispensable for the transcriptional regulation of these genes by LPS. In summary, these results suggest that both NF-kappaB-dependent and NF-kappaB-independent pathways are necessary for the induction by LPS of a complex cytokine and chemokine response. In the RAW264.7 macrophage cell line, suprapharmacological concentrations of sodium salicylate exert a potent inhibitory effect on LPS-induced cytokine gene induction but appear to accomplish this by interfering with NF-kappaB-independent pathways of activation.
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PMID:Inhibition of cytokine gene expression by sodium salicylate in a macrophage cell line through an NF-kappaB-independent mechanism. 1039 64

The cellular infiltration found during CNS inflammation consists of monocytes and activated T cells, suggesting the presence of cell-specific chemotactic signals during inflammatory responses. Astrocyte chemokine expression might contribute to site-specific leukocyte infiltration within the CNS. To investigate the factors that regulate astrocyte chemokine expression, we examined the ability of human fetal astrocytes to induce beta-family chemokine mRNA. Astrocyte-derived monocyte chemoattractant protein-1 (MCP-1), RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta mRNA were easily induced by lipopolysaccharide and/or the proinflammatory cytokines (IFN-gamma and/or TNF-alpha), respectively. Addition of both IFN-gamma and TNF-alpha together did not lead to an additive effect but resulted in the inhibition of MCP-1 and MIP-1beta mRNA expression, indicating that interaction between chemokines and cytokines may play a key role in regulating the local immune response of resident and infiltrating cells at the site of lesion. Interestingly, ultraviolet light-inactivated measles virus, but not cytomegalovirus, strongly induced expression of MCP-1, RANTES, MIP-1alpha, and MIP-1beta mRNA in human embryonic astrocytes, especially MCP-1 and MIP-1beta. An association occurs between the beta-family chemokine expression in astrocytes and inflammatory factors/virus, suggesting a possible role for beta-family chemokines in the pathogenesis of CNS inflammatory disease.
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PMID:Induction of beta-family chemokines mRNA in human embryonic astrocytes by inflammatory cytokines and measles virus protein. 1040 24

Bacterial infections are characterized by strong inflammatory reactions. The responsible mediators are often bacterially derived cell wall molecules, such as lipopolysaccharide or lipoteichoic acids, which typically stimulate monocytes and macrophages to release a wide variety of inflammatory cytokines and chemokines. Mycoplasmas, which lack a cell wall, may also stimulate monocytes very efficiently. This study was performed to identify mycoplasma-induced mediators. We investigated the induction of cytokines and chemokines in human monocytes exposed to the Mycoplasma fermentans-derived membrane component MALP-2 (macrophage-activating lipopeptide 2) by dose response and kinetic analysis. We found a rapid and strong MALP-2-inducible chemokine and cytokine gene expression which was followed by the release of chemokines and cytokines with peak levels after 12 to 20 h. MALP-2 induced the neutrophil-attracting CXC chemokines interleukin-8 (IL-8) and GRO-alpha as well as the mononuclear leukocyte-attracting CC chemokines MCP-1, MIP-1alpha, and MIP-1beta. Production of the proinflammatory cytokines tumor necrosis factor alpha and IL-6 started at the same time as chemokine release but required 10- to 100-fold-higher MALP-2 doses. The data show that the mycoplasma-derived lipopeptide MALP-2 represents a potent inducer of chemokines and cytokines which may, by the attraction and activation of neutrophils and mononuclear leukocytes, significantly contribute to the inflammatory response during mycoplasma infection.
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PMID:Induction of cytokines and chemokines in human monocytes by Mycoplasma fermentans-derived lipoprotein MALP-2. 1056 41

Earlier studies have supported a significant role for cocaine in the susceptibility to and the progression of human immunodeficiency virus type 1 (HIV-1) infection. Recently, several unique HIV-1 entry coreceptors (e.g., CCR5 and CCR3) and a trio of HIV-1-specific suppressor chemokines, namely, RANTES (regulated-upon-activation T expressed and secreted), macrophage inflammatory protein 1alpha (MIP-1alpha) and MIP-1beta, were identified. Although cocaine has been linked to the immunopathogenesis of HIV-1 infection, the corresponding cellular and molecular mechanism(s) have not been well defined. We hypothesize that cocaine mediates these pathologic effects through the downregulation of HIV-1-suppressing chemokines and/or upregulating HIV-1 entry coreceptors in HIV-1-infected subjects, resulting in disease progression to AIDS. Our results show that cocaine selectively downregulates endogenous MIP-1beta secretion by normal peripheral blood mononuclear cells (PBMC), while cocaine did not affect the MIP-1beta production by PBMC from AIDS patients. Cocaine also selectively suppresses lipopolysaccharide-induced MIP-1beta production by PBMC from HIV-infected patients. Further, cocaine significantly downregulates endogenous MIP-1beta gene expression, while it upregulates HIV-1 entry coreceptor CCR5 by normal PBMC. These studies suggests a role for cocaine as a cofactor in the pathogenesis of HIV infection and support the premise that cocaine increases susceptibility to and progression of HIV-1 infection by inhibiting the synthesis of HIV-1 protective chemokines and/or upregulating the HIV-1 entry coreceptor, CCR5.
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PMID:Cocaine differentially modulates chemokine production by mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients. 1061 85

Sixteen healthy subjects were intravenously injected with lipopolysaccharide (LPS), once with placebo and once with recombinant human interleukin (IL)-10 (25 microgram/kg), to determine the effect of IL-10 on LPS-induced production of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1. LPS induced transient increases in serum MIP-1alpha, MIP-1beta, and MCP-1. Pretreatment with IL-10 inhibited LPS-induced release of MIP-1alpha, MIP-1beta, and MCP-1. In whole blood in vitro, the IL-10-induced inhibition of MIP-1alpha and MIP-1beta release was equally potent in the presence or absence of an anti-tumor necrosis factor (TNF) antibody. Although isolated peripheral blood mononuclear cells produced more MIP-1alpha and MIP-1beta than neutrophils, the latter cells were more sensitive to the inhibiting effect of IL-10. IL-10 attenuates LPS-induced production of CC chemokines in human endotoxemia, whereby in vitro experiments suggest that, in the case of MIP-1alpha and MIP-1beta release, this effect is independent from an inhibitory effect on TNF production.
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PMID:Interleukin 10 inhibits the release of CC chemokines during human endotoxemia. 1066 45

Bacterial lipopolysaccharide (LPS) has been shown to induce a wide variety of pro-inflammatory cytokines and chemokines. An initial challenge with minute amounts of LPS causes tolerance to later LPS effects which is characterized by a much lower or abrogated release of pro-inflammatory cytokines. To explore the relationship between the production of chemokines and the induction of LPS tolerance, we pretreated human monocytes with increasing LPS doses and thereafter restimulated with LPS. The re-expression of the CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES was substantially suppressed after pre-incubation with low LPS doses. In striking contrast, the re-expression of neutrophil-attracting IL-8 and melanoma growth stimulatory activity-alpha and of the monocyte-attracting monocyte chemotactic protein-1 remained high and was, in part, initially increased after restimulation with LPS. The corresponding gene expression pattern as determined by Northern blot analyses correlated closely with the release of chemokines and cytokines. Thus, a basic set of chemotactic mediators that are still produced by otherwise LPS-desensitized monocytes/macrophages may ensure the continuing recruitment of monocytes and neutrophils into an inflammatory process caused by gram-negative bacteria.
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PMID:Differential desensitization of lipopolysaccharide-inducible chemokine gene expression in human monocytes and macrophages. 1089 91

Cholera toxin (CT) is a potent mucosal adjuvant that amplifies B and T cell responses to mucosally co-administered antigens, stimulating predominant Th2-type responses. However, little is known about the mechanism of adjuvanticity of CT and on the influence this toxin may have on Th2 cell development during the priming of an immune response. We analyzed the effect of CT on dendritic cells (DC), which are responsible for the priming of immune responses at the systemic as well as at the mucosal level. We found that CT induces phenotypic and functional maturation of blood monocyte-derived DC. Indeed, CT-treated DC up-regulate expression of HLA-DR molecules, B7. 1 and B7.2 co-stimulatory molecules, and are able to prime naive CD4(+)CD45RA(+) T cells in vitro, driving their polarization towards the Th2 phenotype. Furthermore, CT-matured DC express functional chemokine receptors CCR7 and CXCR4 which may render them responsive to migratory stimuli towards secondary lymphoid organs. Interestingly, the maturation program induced by CT is unique since CT does not induce but rather inhibits cytokine (IL-12p70 and TNF-alpha) and chemokine (RANTES, MIP-1alpha and MIP-1beta) secretion by lipopolysaccharide- or CD40 ligand-activated DC. Our results help to elucidate the mechanism of action of CT as an adjuvant and highlight a new stimulus of bacterial origin that promotes maturation of DC.
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PMID:Cholera toxin induces maturation of human dendritic cells and licences them for Th2 priming. 1094 Sep 31

Concurrent infections in patients with human immunodeficiency virus (HIV) infection stimulate HIV replication. Chemokine receptors CXCR4 and CCR5 can act as HIV coreceptors. The authors hypothesized that concurrent infection increases the HIV load through up-regulation of CXCR4 and CCR5. Using experimental endotoxemia as a model of infection, changes in HIV coreceptor expression were assessed in 8 subjects injected with lipopolysaccharide (LPS, 4 ng/kg). The expression of CXCR4 and CCR5 on CD4(+) T cells was increased 2- to 4-fold, 4 to 6 hours after LPS injection. In whole blood in vitro, LPS induced a time- and dose-dependent increase in the expression of CXCR4 and CCR5 on CD4(+) T cells. Similar changes were observed after stimulation with cell wall components of Mycobacterium tuberculosis (lipoarabinnomannan) or Staphylococcus aureus (lipoteichoic acid), or with staphylococcal enterotoxin B. LPS increased viral infectivity of CD4-enriched peripheral blood mononuclear cells (PBMCs) with a T-tropic HIV strain. In contrast, M-tropic virus infectivity was reduced, possibly because of elevated levels of the CCR5 ligand cytokines RANTES and MIP-1beta. LPS-stimulated up-regulation of CXCR4 and CCR5 in vitro was inhibited by anti-TNF and anti-IFN gamma. Incubation with recombinant TNF or IFN gamma mimicked the LPS effect. Anti-interleukin 10 (anti-IL-10) reduced CCR5 expression, without influencing CXCR4. In accordance, rIL-10 induced up-regulation of CCR5, but not of CXCR4. Intercurrent infections during HIV infection may up-regulate CXCR4 and CCR5 on CD4(+) T cells, at least in part via the action of cytokines. Such infections may favor selectivity of HIV for CD4(+) T cells expressing CXCR4. (Blood. 2000;96:2649-2654)
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PMID:Up-regulation of HIV coreceptors CXCR4 and CCR5 on CD4(+) T cells during human endotoxemia and after stimulation with (myco)bacterial antigens: the role of cytokines. 1102 94

As the first line of defense against inhaled substances, alveolar macrophages (AM) play a crucial role in maintaining lung homeostasis. This is achieved via phagocytosis of foreign material and the secretion of a wide range of mediator molecules, including those involved in neutrophil recruitment. Neonates are known to manifest increased susceptibility to lung infections, and we hypothesize that this may be due in part to a deficiency in the function of AM. We report here that although recruitment of neutrophils into the respiratory tract of newborn animals in response to Moraxalla catarrhalis exposure is greatly delayed and diminished, AM from newborn animals have greater phagocytic capacity when compared with those from adult animals. Additionally, newborn AM respond normally to lipopolysaccharide (LPS) via production of a variety of chemokines, including macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, monocyte chemotactic protein-1, gro/ cytokine-induced neutrophil chemoattractant, MIP-2, and tumor necrosis factor-alpha. We have also demonstrated an LPS inducible expression of messenger RNA for LPS binding protein (LBP) in neonatal AM that was not observed in AM from adult animals or in peritoneal macrophages. We speculate that local production of LBP by AM may be a significant factor in the neonatal immunologic response to infections, providing a compensatory mechanism for the deficiency in specific neonatal immunity during this period of development when the newborn is being exposed to a range of potentially pathogenic materials for the first time.
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PMID:Role of alveolar macrophages in innate immunity in neonates: evidence for selective lipopolysaccharide binding protein production by rat neonatal alveolar macrophages. 1106 44


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