Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autotaxin, a lysophospholipase D producing lysophosphatidic acid, augments invasive and metastatic potential of tumor cells. Current investigations have focused on understanding the molecular mechanisms by which autotaxin regulates the expression of a major mediator of tumor invasion and metastasis, urokinase-type plasminogen activator (uPA) in human A2058 melanoma cells. Autotaxin induced uPA expression in a dose-dependent manner that was inhibited by pharmacological inhibitors for Gi (pertussis toxin), phosphoinositide 3-kinase (PI3K, LY294002), Akt inhibitor (AktI), proteosome activity and IkappaB phosphorylation (pyrrolidine dithiocarbamate), and by a dominant negative mutant (DN) of Akt. Autotaxin phosphorylated Akt and induced the translocation of nuclear [corrected] factor-kappaB (NF-kappaB) to the nucleus that were inhibited by AktI or by overexpressing DN-Akt. Consistently, green fluorescence protein-tagged p65 of NF-kappaB accumulated in the nucleus by autotaxin that was abrogated when the cells were transfected with DN-Akt. Moreover, autotaxin increased the DNA binding ability of NF-kappaB and promoter activity of uPA. Collectively, these data strongly suggest autotaxin induces uPA expression via the Gi-PI3K-Akt-NF-kappaB signaling pathway that might be critical for autotaxin-induced tumor cell invasion and metastasis.
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PMID:Autotaxin stimulates urokinase-type plasminogen activator expression through phosphoinositide 3-kinase-Akt-nuclear [corrected] factor kappa B signaling cascade in human melanoma cells. 1701 94

As a transmembrane chemokine, CXCL16 has been detected in various tissues and organs under normal and pathological conditions, it also plays an important role in macrophages/dendritic cells (DC) and T cell interactions and trafficking during inflammation and immune responses. LysoPtdOH, a bioactive lipid mediator has been indicated to regulate DC and epithelial functions during wound healing and inflammation responses. However, the direct link of CXCL16 expression with lysoPtdOH has not been established. Using monocyte-derived macrophages/DC (MoDC), we investigated the roles of lysoPtdOH in CXCL16 production and cell surface presentation. We found that macrophages/MoDC constitutively express and secrete CXCL16, lysoPtdOH significantly enhanced CXCL16 protein production stimulated with lipopolysaccharide (LPS) by more than twofold, which was reflected by increased mRNA transcription by 64-fold. Production of CXCL16 increased by lysoPtdOH and LPS from macrophages was inhibited around 70% by Pertussis toxin (G(i/o) specific inhibitor), exoC3 (Rho specific inhibitor), and pyrrolidine dithiocarbamate (the NF-kappaB-dependent pathway inhibitor) separately. LysoPtdOH treatment increased macrophages' chemotactic activity to activated T cells. The soluble form of CXCL16 produced by macrophages/MoDC was functionally chemoattractive to T cells.
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PMID:LysoPtdOH enhances CXCL16 production stimulated by LPS from macrophages and regulates T cell migration. 1883 Jul 32

Neurodegenerative and neuroinflammatory disorders are commonly associated with local chemokine release. In other way, emerging data indicate that the prostaglandin E2 (PGE(2)), one of the major prostaglandins produced in the brain, play a central role in several pathological diseases. In this study, we investigated the relationship between CXCL12, cyclooxygenase (COX)-2 and PGE(2) in human brain cells. CXCL12 induced COX-2 and secretion of PGE(2) in a dose-dependent manner in human astrocytes. This induction was abolished by treatment with pertussis toxin and AMD3100, confirming the role of CXCR4 signaling. The nuclear factor-kappaB involvement was confirmed by using pyrrolidine dithiocarbamate, and with transient transfection assays. Over-expression of inhibitory proteins of nuclear factor-kappaB abrogated COX-2 induction, and CXCL12 induced p65/relA translocation. Culture supernatants from CXCL12-treated astrocytes reduced viability of neuroblastoma cells, and COX inhibitors abrogated this toxicity. Therefore, the relationship between chemokines and PGs could differentially influence the pathogenic network responsible for neurodegeneration.
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PMID:Nuclear factor-kappaB activation regulates cyclooxygenase-2 induction in human astrocytes in response to CXCL12: role in neuronal toxicity. 2018 Aug 83


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