期刊
JOURNAL OF LIPID RESEARCH
卷 46, 期 5, 页码 1027-1037出版社
ELSEVIER
DOI: 10.1194/jlr.M500006-JLR200
关键词
macrophage; lipopolysaccharide; cyclooxygenase-1; cyclooxygenase-2; arachidonic acid; cytosolic phospholipase A(2)
Studies of the response of RAW264.7 cells ( RAW) to lipopolysaccharide (LPS) were carried out to determine why these cells do not demonstrate the prostaglandin (PG)dependent autocrine regulation of tumor necrosis factor-alpha (TNF-alpha) secretion observed in primary resident peritoneal macrophages (RPMs). The major cyclooxygenase (COX) product of LPS-stimulated RAW was PGD(2), with lesser amounts of PGE(2). LPS-treated RAW produced PGs more slowly and reached their maximal PG synthetic rate later than did LPS-treated RPMs, as a result of lower constitutive COX-1 expression and a slower rate of COX-2 induction. Cytosolic phospholipase A(2) and levels of free arachidonic acid were similar in RAW and RPMs. In contrast to RPMs, LPS-treated RAW produced high quantities of TNF-alpha, which were not altered in the presence of COX inhibitors. This failure of endogenous PGs to suppress TNF-alpha secretion was explained by the absence of the prostaglandin D-2 receptor and the low levels of PGE(2) produced during the first 2 h of the LPS response. These studies demonstrate that autocrine regulation of TNF-alpha secretion in response to LPS is greatly facilitated by a COX-1-mediated rapid accumulation of PGs as well by a correspondence between the PGs produced and the receptors expressed by the cells.
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