Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocytes play an important role in inflammation, angiogenesis, and atherosclerosis. During these processes monocytes release pre-formed proinflammatory mediators from granules, and synthesize de novo cytokines and chemokines important in the amplification of the inflammatory response. One of the most prominent triggers of inflammatory responses is the cytokine TNFalpha. However, the intracellular signaling cascades triggered by TNFalpha are not fully understood. In this study we investigated the roles of SPHK on the TNFalpha-triggered responses on human primary monocytes. We show that TNFalpha rapidly triggers S1P generation and activation of SPHK. Moreover, our data shows that SPHK1 is the isoform activated by TNFalpha, and plays an essential role on the TNFalpha-triggered intracellular Ca2+ signals, degranulation, cytokine production, and activation of NFkappaB, thus suggesting a pivotal role for SPHK1 on the proinflammatory responses triggered by TNFalpha.
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PMID:Sphingosine kinase 1 regulates pro-inflammatory responses triggered by TNFalpha in primary human monocytes. 2253 99

TNFα stimulates SPHK in the monocyte, which leads to the expression of adhesion molecules on the cell surface. The adhesion of leukocytes to the endothelium is one of the early stages of the onset of atherosclerosis. In this paper, we have delineated the TNFα-induced and SPHK-dependent signaling pathway. In addition, we have developed a biomathematical model to qualify the SPHK time-dependent activity at a specific site in the cell upon TNFα stimulation. Thus, this study provides a biochemical and mechanistic approaches to the understanding of leukocyte-endothelial attachment, so that measures could be designed to minimize the onset of atherosclerosis.
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PMID:Role of sphingosine kinase in the expression of adhesion molecules on monocytes induced by tumor necrosis factor-alpha (relevant to atherosclerosis). 1728 13