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)

Rat cytokine-induced neutrophil chemoattractants (CINCs) are the members of the CXC chemokine family. Four neutrophil chemokines, CINC-1, CINC-2 alpha, CINC-2 beta and CINC-3, were purified from the conditioned medium of granulation-tissue culture. CINC-2 alpha and CINC-2 beta differ only in the sequence of three carboxy-terminal residues and are produced by alternative splicing. CINC-3 had neutrophil chemotactic activity similar to that of CINC-1 and CINC-2, but induced greater calcium mobilization than CINC-1 and CINC-2. CINC-1, -2 and -3 induced calcium flux in CXCR2-transfected HEK293 cells. In addition, anti-CXCR2 serum inhibited neutrophil chemotactic activities of the three types of CINCs almost completely. These results indicate that rat CXCR2 is a unique receptor for CINC-1, -2 and -3. CINCs induced calcium mobilization through pertussis toxin-insensitive G-protein but induced chemotaxis through pertussis toxin-sensitive G-protein. CINC-1/-2 and CINC-3 may stimulate both G-proteins with distinct efficiency. The concentration of CINC-1 increased transiently in rat air pouch/lipopolysaccharide inflammation, whereas the CINC-2 level increased linearly. The number of infiltrated cells increased up to 8 h. The increase in cell number was correlated with the total concentration of CINC-1 and CINC-2. Northern blot analyses and enzyme-linked immunosorbent assay showed that CINC expression was very low in rat macrophages without stimulation and increased after lipopolysaccharide stimulation. These data suggest that CINCs are expressed by inflammatory cells such as macrophages at a site of inflammation and play important roles in neutrophil infiltration.
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PMID:[The role of rat cytokine-induced neutrophil chemoattractants (CINCs) in inflammation]. 1196 38

The interactions of Neisseria meningitidis with cells of the leptomeninges are pivotal events in the progression of bacterial leptomeningitis. An in vitro model based on the culture of human meningioma cells was used to investigate the role of the leptomeninges in the inflammatory response. Following challenge with meningococci, meningioma cells secreted specifically the proinflammatory cytokine interleukin-6 (IL-6), the CXC chemokine IL-8, the CC chemokines monocyte chemoattractant protein 1 (MCP-1) and regulated-upon-activation, normal-T-cell expressed and secreted protein (RANTES), and the cytokine growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). A temporal pattern of cytokine production was observed, with early secretion of IL-6, IL-8, and MCP-1 followed by later increases in RANTES and GM-CSF levels. IL-6 was induced equally by the interactions of piliated and nonpiliated meningococci, whereas lipopolysaccharide (LPS) had a minimal effect, suggesting that other, possibly secreted, bacterial components were responsible. Induction of IL-8 and MCP-1 also did not require adherence of bacteria to meningeal cells, but LPS was implicated. In contrast, efficient stimulation of RANTES by intact meningococci required pilus-mediated adherence, which served to deliver increased local concentrations of LPS onto the surface of meningeal cells. Secretion of GM-CSF was induced by pilus-mediated interactions but did not involve LPS. In addition, capsule expression had a specific inhibitory effect on GM-CSF secretion, which was not observed with IL-6, IL-8, MCP-1, or RANTES. Thus, the data demonstrate that cells of the leptomeninges are not inert but are active participants in the innate host response during leptomeningitis and that there is a complex relationship between expression of meningococcal components and cytokine induction.
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PMID:Interaction of Neisseria meningitidis with human meningeal cells induces the secretion of a distinct group of chemotactic, proinflammatory, and growth-factor cytokines. 1211 9

The chemoattractant stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) are key modulators of immune function. In the developing brain, SDF-1 is crucial for neuronal guidance; however, cerebral functions of SDF-1/CXCR4 in adulthood are unclear. Here, we examine the cellular expression of SDF-1 isoforms and CXCR4 in the brain of mice receiving systemic lipopolysaccharide (LPS) or permanent focal cerebral ischemia. CXCR4 mRNA was constitutively expressed in cortical and hippocampal neurons and ependymal cells. Hippocampal neurons targeted the CXCR4 receptor to their somatodendritic and axonal compartments. In cortex and hippocampus, CXCR4-expressing neurons exhibited an overlapping distribution with neurons expressing SDF-1 transcripts. Although neurons synthesized SDF-1alpha mRNA, the SDF-1beta isoform was selectively expressed by endothelial cells of cerebral microvessels. LPS stimulation dramatically decreased endothelial SDF-1beta mRNA expression throughout the forebrain but did not affect neuronal SDF-1alpha. After focal cerebral ischemia, SDF-1beta expression was selectively increased in endothelial cells of penumbral blood vessels and decreased in endothelial cells of nonlesioned brain areas. In the penumbra, SDF-1beta upregulation was associated with a concomitant infiltration of CXCR4-expressing peripheral blood cells, including macrophages. Neuronal SDF-1alpha was transiently downregulated and neuronal CXCR4 was transiently upregulated in the nonlesioned cerebral cortex in response to ischemia. Although endothelial SDF-1beta may control cerebral infiltration of CXCR4-carrying leukocytes during cerebral ischemia, the neuronal SDF-1alpha/CXCR4 system may contribute to ischemia-induced neuronal plasticity. Thus, the isoform-specific regulation of SDF-1 expression modulates neurotransmission and cerebral infiltration via distinct CXCR4-dependent pathways.
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PMID:A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. 1212 49

Neurons are often assumed to be the principal sites for replication of the infectious agents causing Creutzfeldt-Jakob disease (CJD), scrapie, and bovine spongiform encephalopathy because they express high levels of normal and pathological prion protein (PrP). However, isolated brain cell types have not been evaluated for either infection or gene expression. Microglia purified from CJD-infected mice showed infectivity comparable to that of starting brain homogenate but expressed approximately 50-fold less PrP. CJD-infected microglia also displayed morphological changes indicative of cellular activation. To determine the molecular pathways of activation, we evaluated pertinent transcripts, including those linked to inflammation. Semiquantitative reverse transcription-PCR showed a >4-fold increase in cathepsin S, an enzyme important in antigen presentation, the cytokine interleukin-1beta, and the chemokine B-lymphocyte chemoattractant. The profile of microglial changes induced by the CJD agent differed substantially from activation induced by bacterial lipopolysaccharide or by beta-amyloid, a structure comparable to pathological PrP. These microglial studies emphasize migratory hematopoietic cells in the dispersion, and possibly replication, of the CJD agent. The low PrP levels in these highly infectious and activated cells further support the concept that pathological PrP is the result of infection rather than the infectious agent itself. Because microglia develop a specific pattern of responses to the CJD agent, microglial markers may be exploited in the diagnosis of these spongiform encephalopathies.
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PMID:Microglia from Creutzfeldt-Jakob disease-infected brains are infectious and show specific mRNA activation profiles. 1236 33

It is well established that cytokines can induce the production of chemokines, but the role of chemokines in the regulation of cytokine expression has not been fully investigated. Exposure of rat cardiac-derived endothelial cells (CDEC) to lipopolysaccharide-induced CXC chemokine (LIX), and to a lesser extent to KC and MIP-2, activated NF-kappaB and induced kappaB-driven promoter activity. LIX did not activate Oct-1. LIX-induced interleukin-1beta and tumor necrosis factor-alpha promoter activity, and up-regulated mRNA expression. Increased transcription and mRNA stability both contributed to cytokine expression. LIX-mediated cytokine gene transcription was inhibited by interleukin-10. Transient overexpression of kinase-deficient NF-kappaB-inducing kinase (NIK) and IkappaB kinase (IKK), and dominant negative IkappaB significantly inhibited LIX-mediated NF-kappaB activation in rat CDEC. Inhibition of G(i) protein-coupled signal transduction, poly(ADP-ribose) polymerase, phosphatidylinositol 3-kinase, and the 26 S proteasome significantly inhibited LIX-mediated NF-kappaB activation and cytokine gene transcription. Blocking CXCR2 attenuated LIX-mediated kappaB activation and kappaB-driven promoter activity in rat CDEC that express both CXCR1 and -2, and abrogated its activation in mouse CDEC that express only CXCR2. These results indicate that LIX activates NF-kappaB and induces kappaB-responsive proinflammatory cytokines via either CXCR1 or CXCR2, and involved phosphatidylinositol 3-kinase, NIK, IKK, and IkappaB. Thus, in addition to attracting and activating neutrophils, the ELR(+) CXC chemokines amplify the inflammatory cascade, stimulating local production of cytokines that have negative inotropic and proapoptotic effects.
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PMID:Chemokine-cytokine cross-talk. The ELR+ CXC chemokine LIX (CXCL5) amplifies a proinflammatory cytokine response via a phosphatidylinositol 3-kinase-NF-kappa B pathway. 1246 47

CXC chemokines are major chemoattractants for pulmonary polymorphonuclear leukocyte (PMNL) recruitment. To study the effects of interferon (IFN)-gamma on the pulmonary chemokine response to lipopolysaccharide (LPS) challenge, rats were treated with intratracheal IFN-gamma (1x10(5) U/rat) 24 h before an intratracheal LPS (100 microg/rat) challenge. Intratracheal LPS caused significant increases in both cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 in bronchoalveolar lavage (BAL) fluid and pulmonary PMNL recruitment. IFN-gamma enhanced these responses. IFN-gamma also increased LPS-induced tumor necrosis factor (TNF)-alpha in BAL fluid. LPS-induced TNF-alpha and CINC mRNA expression in alveolar macrophages was increased by IFN-gamma. CD11b/c and CD18 expression on circulating PMNLs was not affected by IFN-gamma, nor was the chemotaxis of these cells. IFN-gamma increases the pulmonary CXC chemokine response, which may serve as one mechanism underlying enhanced PMNL delivery into the lung.
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PMID:Interferon-gamma enhances the pulmonary CXC chemokine response to intratracheal lipopolysaccharide challenge. 1250 47

Human granulocyte chemotactic protein-2 (GCP-2)/CXCL6 is a CXC chemokine that functionally uses both of the IL-8/CXCL8 receptors to chemoattract neutrophils but that is structurally most related to epithelial cell-derived neutrophil attractant-78 (ENA-78)/CXCL5. This study provides the first evidence that GCP-2 protein is, compared with IL-8, weakly produced by some sarcoma, but less by carcinoma cells, and is tightly regulated in normal mesenchymal cells. IL-1beta was the predominant GCP-2 inducer in fibroblasts, chondrocytes, and endothelial cells, whereas IL-8 was equally well up-regulated in these cells by TNF-alpha, measles virus, or double-stranded RNA (dsRNA). In contrast, lipopolysaccharide (LPS) was a relatively better stimulus for GCP-2 versus IL-8 in fibroblasts. IFN-gamma down-regulated the GCP-2 production in fibroblasts induced by IL-1beta, TNF-alpha, LPS, or dsRNA. The kinetics of GCP-2 induction by IL-1beta, LPS, or dsRNA in fibroblasts differed from those of IL-8. Freshly isolated peripheral blood mononuclear leukocytes, which are a good source of IL-8 and ENA-78, failed to produce GCP-2. However, lung macrophages and blood monocyte-derived macrophages produced GCP-2 in response to LPS. Quantitatively, secretion of GCP-2 always remained inferior to that of IL-8, despite the fact that the ELISA recognized all posttranslationally modified GCP-2 isoforms. The expression of GCP-2 was confirmed in vivo by immunohistochemistry. The patterns of producer cell types, inducers and kinetics and the quantities of GCP-2 produced, suggest a unique role for GCP-2 in physiologic and pathologic processes.
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PMID:The CXC chemokine GCP-2/CXCL6 is predominantly induced in mesenchymal cells by interleukin-1beta and is down-regulated by interferon-gamma: comparison with interleukin-8/CXCL8. 1253 83

In this paper, we describe the role of chemokine receptor CXCR4 activation by its natural ligand, the chemokine stromal cell-derived factor (SDF-1) (CXCL12), in glioblastoma cell growth in vitro. We show that both CXC chemokine receptor 4 (CXCR4) and SDF-1 mRNA are expressed in several human glioblastoma multiforme tumor tissues and in two human glioblastoma cell lines, U87-MG and DBTRG-05MG. These cells are able to secrete SDF-1 under basal conditions, and the rate of secretion is highly increased after lipopolysaccharide or 1% fetal bovine serum treatment. Exogenous SDF-1alpha induces proliferation in a dose-dependent manner in both cell lines. Moreover, we observed that SDF-1alpha-dependent proliferation is correlated with phosphorylation and activation of both extracellular signal-regulated kinases 1/2 and Akt and that these kinases are independently involved in glioblastoma cell proliferation. The role of CXCR4 stimulation in glioblastoma cell growth is further demonstrated by the ability of human monoclonal CXCR4 antibody (clone 12G5) to inhibit the SDF-1alpha-induced proliferation as well as the proliferation induced by SDF-1-releasing treatments (lipopolysaccharide and 1% fetal bovine serum). These data support a role for SDF-1alpha in the regulation of glioblastoma growth in vitro, likely through an autocrine/paracrine mechanism.
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PMID:Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt. 1270 90

CXC chemokines, structurally recognizable by the position of four conserved cysteine residues, are prominent mediators of chemotaxis. Here we report a novel carp CXC chemokine obtained through homology cloning and compare it with fish orthologues genes and with a second, recently elucidated, carp CXC chemokine. Phylogenetic analyses clearly show that neither CXC chemokine resembles any of the mammalian CXC chemokines in particular. However, basal expression is most prominent in immune organs like anterior kidney and spleen, suggesting involvement in the immune response. Furthermore we show that anterior kidney phagocyte-enriched leukocyte suspensions express both chemokines and that this expression is upregulated by brief (4 h) stimulation with PMA, but not lipopolysaccharide. Neutrophilic granulocyte-enriched leukocytes display chemotaxis to human recombinant CXCL8 (hrCXCL8; interleukin-8), confirming CXC chemokine mediated chemotaxis of neutrophilic granulocytes in teleost fish. Factors secreted from carp phagocytes are also capable of inducing chemotaxis and secretion of these factors into culture supernatants is upregulated by PMA. Finally we demonstrate involvement of both CXC chemokines as well as CXCR1 and CXCR2 in acute Argulus japonicus infection. Collectively the data presented implicate the involvement of CXC chemokines in chemotaxis of fish neutrophils in a fashion that shares characteristics with the mammalian situation. However, the CXC chemokines involved differ enough from those involved in neutrophil chemotaxis in mammals to warrant their own nomenclature.
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PMID:CXC chemokines and leukocyte chemotaxis in common carp (Cyprinus carpio L.). 1288 Jun 37

Platelet factor 4 (PF4) is a CXC chemokine secreted by activated platelets. PF4 has been shown to promote monocyte survival and induce the differentiation of monocytes into macrophages. However, the effect of PF4 on differentiation of monocytes into dendritic cells (DC) has yet to be determined. As reported previously, monocytes cultured in RPMI medium containing FCS, granulocyte macrophage colony stimulating factor and IL-4 differentiated into CD1a+ DC. When PF4 was added, the expression of CD1a on DC was inhibited. This inhibitory effect was not observed with the other platelet-derived CXC chemokine, beta-thromboglobulin. The relative number of CD1a- DC increased from 17 to 92% when the PF4 concentration was increased from 0 to 10 micro g/ml. The inhibitory effect of PF4 on CD1a expression was reversed by 50 U/ml heparin. DC developed in the PF4-containing media appeared more adhesive to plastic culture wells and had higher light side scatter by flow cytometry. Immunophenotypically, monocyte-derived DC in the presence of increasing concentrations of PF4 proportionally expressed higher CD86 and lower HLA-DR. The levels of CD11c, CD40 and CD80 remained unchanged with or without PF4. Both CD1a+ DC and CD1a- DC were negative for CD14, CD68 and CD83. Functionally, DC developed in the presence of PF4 had their secretion of tumor necrosis factor-alpha and IL-12 reduced by 75 +/- 10 and 79 +/- 13% respectively when they were stimulated by 100 ng/ml lipopolysaccharide and 50 ng/ml IFN-gamma. CD1a- DC developed in the presence of PF4 were not as active as the control CD1a+ DC in stimulating allogeneic T cells to proliferate. In addition, CD1a- DC were less potent in priming naive CD4+ T cells to secrete both type 1 and 2 cytokines. These results indicate that PF4 can influence differentiation and function of monocyte-derived DC.
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PMID:Effect of CXC chemokine platelet factor 4 on differentiation and function of monocyte-derived dendritic cells. 1288 38


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