Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The novel colony-stimulating factor (CSF) inducer leustroducsin B (LSN-B), which was isolated from Streptomyces platensis, has been shown to have potent cytokine-inducing activities in clonal human bone marrow-derived stromal cell line KM-102 and in primary human bone marrow-derived stromal cells. In this study, we investigated the signal transduction pathway of LSN-B using luciferase expression plasmids linked to the 5'-flanking region of interleukin-8 (IL-8) and that of the IL-11 gene. In KM-102 cells, LSN-B induced luciferase activity both in the wild-type and in the activated protein 1 (AP-1) site point-mutated IL-8 promoter. The mutation in the nuclear factor-kappaB (NF-kappaB) site abrogated LSN-B-stimulated induction of the reporter gene. LSN-B-inducing activity was inhibited by (1) N-acetyl-L-cysteine, a well-characterized antioxidant, (2) cationic amphiphilic drugs, inhibitors of acidic sphingomyelinase (A-SMase), and (3) D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC). These observations suggest that LSN-B potentiates the A-SMase-mediated signaling pathway to stimulate NF-kappaB. In contrast, LSN-B did not induce IL-11 promoter-driven luciferase activity. The observed increase in IL-11 mRNA stability by LSN-B indicates that the inducible production of IL-11 by LSN-B is regulated at the posttranscriptional level. In addition, inhibition of LSN-B-mediated induction of IL-11 production by cationic amphiphilic drugs and D609 in KM-102 cells demonstrates that increased IL-11 mRNA stability by LSN-B might be mediated via NF-kappaB activation. From these results, we suggest that LSN-B induces cytokine production through at least two separate mechanisms, at the transcriptional level and at the posttranscriptional level via NF-kappaB activation.
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PMID:Leustroducsin B activates nuclear factor-kappaB via the acidic sphingomyelinase pathway in human bone marrow-derived stromal cell line KM-102. 1203 42

Prokineticin 1 (PROK1) is a recently described protein with a wide range of functions including tissue-specific angiogenesis, modulation of inflammatory responses, and regulation of hematopoiesis. The objective of this study was to investigate the role of PROK1 and prokineticin receptor 1 (PROKR1) in human endometrium during early pregnancy. PROK1 and PROKR1 expression is significantly elevated in first-trimester decidua, compared with nonpregnant endometrium. Expression of PROK1 and PROKR1 was localized in glandular epithelial and various cellular compartments within the stroma. To investigate the signaling pathways and target genes activated by PROK1, we generated an endometrial epithelial cell line stably expressing PROKR1 (Ishikawa PROKR1 cells). PROK1-PROKR1 interaction induced inositol phosphate mobilization and sequential phosphorylation of c-Src, epidermal growth factor receptor, and ERK 1/2. Gene microarray analysis on RNA extracted from Ishikawa PROKR1 cells treated with 40 nm PROK1 for 8 h revealed 49 genes to be differentially regulated. A number of these genes, including cyclooxygenase (COX)-2, leukemia inhibitory factor, IL-6, IL-8, and IL-11 are regulated in the endometrium during implantation and early pregnancy. We subsequently investigated the effect of PROK1 on expression of COX-2 in Ishikawa PROKR1 cells and first-trimester decidua. COX-2 mRNA and protein expression, and prostaglandin synthesis, were elevated in response to treatment with PROK1. Moreover, expression of COX-2 by PROK1 was dependent on activation of the Gq-phospholipase C-beta-cSrc-epidermal growth factor receptor-MAPK/ERK kinase pathway. These data demonstrate that PROK1 and PROKR1 expression is elevated in human decidua during early pregnancy and that PROK1-PROKR1 interaction regulates expression of a host of implantation-related genes.
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PMID:Prokineticin 1 signaling and gene regulation in early human pregnancy. 1833 12