Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autotaxin (ATX/NPP2) is a tumor cell motility-stimulating factor that displays both a nucleotide pyrophosphatase/phosphodiesterase activity and a recently described lysophospholipase D (lysoPLD) activity. The precise function of ATX in tumor cells and the role of ATX in thyroid carcinoma remains unclear. We have quantified ATX mRNA expression in thyroid carcinoma cell lines and in tissues of patients with thyroid carcinomas. ATX gene activity was significantly higher in undifferentiated anaplastic thyroid carcinoma cell lines (UTC) and tumor tissues as compared to follicular thyroid carcinoma (FTC) cell lines, FTC tissues or goiter tissues that were used as a control. In the thyroid carcinoma cell line 1736, EGF and bFGF stimulated ATX mRNA expression, whereas the cytokines IL-4, IL-1beta and TGF-beta reduced ATX transcriptional levels. FTC-133 cells, stably transfected with an expression vector for ATX, showed a higher lysoPLD activity, a higher proliferation rate and an increased migratory behavior. In addition, ATX also displayed a paracrine stimulatory effect on the motility of different thyroid carcinoma cell lines. Overexpression of ATX in the stably transfected FTC-133 resulted in down-regulation of CD54/ intercellular adhesion molecule-1 (ICAM-1) gene expression and augmented gene activity of the pro-angiogenic chemokine IL-8. We conclude that ATX may be regarded as a new tissue marker for undifferentiated human thyroid carcinoma cells. ATX increases the proliferation and migration of thyroid carcinoma cell lines and may also affect the angiogenic potential of thyroid carcinoma cells. Further studies are needed to provide insight into the role of ATX in the normal and neoplastic thyroid gland.
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PMID:Expression, regulation and function of autotaxin in thyroid carcinomas. 1502 16

Lysophosphatidic acid (LPA) is a pleiotropic phospholipid molecule involved in inflammation, angiogenesis, would healing, and cancer invasion. Whereas serum lysophospholipase D activity increases in women with pregnancy, the role of LPA in pregnancy remains unclear. We investigated the expression of LPA receptors and function of LPA in endometrial stromal cells. Histologically normal endometrium was obtained from surgical specimens of women undergoing hysterectomy for leiomyoma. First-trimester decidua was obtained from women receiving elective termination of pregnancy. We examined the expressions of LPA1, LPA2, and LPA3 receptors in endometrial stromal cells. The effects of LPA on the expression of vascular endothelial growth factor, IL-6, and IL-8 were examined. Signal pathways of LPA were delineated. Functions of secretory angiogenic factors were tested using human endometrial microvascular endothelial cells. Immunoreactivity and mRNA of LPA1 receptors were identified in endometrial stromal cells. LPA enhanced IL-8 expression in a dose- and time-dependent manner, whereas vascular endothelial growth factor or IL-6 expression was not affected by LPA treatment. Mechanistic dissection disclosed that LPA functioned via the Gi protein, MAPK/p38 and nuclear factor-kappaB pathway. LPA-induced IL-8 enhanced migration, permeability, capillary tube formation, and proliferation of human endometrial microvascular endothelial cells. Endometrial stromal cells express LPA1 receptors. Through the LPA1 receptor, LPA induces IL-8 expression via a nuclear factor-kappaB-dependent signal pathway. These results could suggest that LPA may play a role in angiogenesis of endometrium and placenta through induction of IL-8 in endometrial stromal cells during pregnancy.
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PMID:Lysophosphatidic acid mediates interleukin-8 expression in human endometrial stromal cells through its receptor and nuclear factor-kappaB-dependent pathway: a possible role in angiogenesis of endometrium and placenta. 1861 17

The serum lysophospholipase D activity and production of lysophosphatidic acid (LPA) increase in women with pregnancy. The effects of LPA on human placenta tissue remained unclear. We investigate the expression of LPA receptors and function of LPA in human first-trimester trophoblasts. Normal villous trophoblasts were obtained from termination of first-trimester gestation. We examined the expression of LPA receptors in primary culture of trophoblasts and the tissue. The effects of LPA on the expressions of chemokines of trophoblasts were examined using RT-PCR and enzyme immunoassay. We delineate signal pathways of LPA-inducing relevant chemokines in trophoblasts. The secretory chemokines were tested for angiogenic function using human endometrial microvascular endothelial cells and for immunological chemotaxis using decidual natural killer cells and THP-1 monocytes. The results revealed the expression of LPA1 receptors in trophoblast cells. LPA enhanced growth-regulated oncogene (GRO)-alpha, IL-8 and monocyte chemoattractant protein (MCP)-1 expressions in a time- and dose-dependent manner. Mechanistic dissection disclosed that LPA functioned mainly via the LPA1 receptor, Gi protein, various signal mediators of ERK, protein kinase C, p38, Akt, and c-Jun N-terminal kinase, and nuclear factor-kappaB pathways to secrete these chemokines. LPA-induced IL-8 protein secretion of trophoblasts enhanced permeability, migration, proliferation, and capillary tube formation of human endometrial microvascular endothelial cells. LPA-induced GRO-alpha and MCP-1 incited chemotaxis of natural killer cells and monocytes. We demonstrate that LPA mediates trophoblast cells to produce GRO-alpha, IL-8, and MCP-1 via LPA1 receptors and nuclear factor-kappaB-dependent signal pathways. Through LPA-induced chemokine production, human first-trimester trophoblast cells may regulate angiogenesis and innate immune system in early pregnancy.
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PMID:Lysophosphatidic acid up-regulates expression of growth-regulated oncogene-alpha, interleukin-8, and monocyte chemoattractant protein-1 in human first-trimester trophoblasts: possible roles in angiogenesis and immune regulation. 1990 15