Linked Life Data

11201160

Source:http://linkedlifedata.com/resource/pubmed/id/11201160

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-2-2
pubmed:abstractText
Phospholipase A2 receptor (PLA2R) is a type I transmembrane glycoprotein related to the C-type animal lectin family and mediates a variety of biological responses elicited by group IB secretory phospholipase A2 (sPLA2-IB). In the present study, we have shown the evidence that a novel type of sPLA2, sPLA2-X, also acts as one of the high-affinity ligands for mouse PLA2R. We then generated PLA2R-deficient mice and found that the knockout mice exhibited the resistance to an endotoxic shock with reduced plasma levels of proinflammatory cytokines, such as TNF-alpha and IL-1 beta. In situ hybridization analysis revealed that the expression of PLA2R transcript was markedly enhanced in type II alveolar epithelial cells and a subset of splenic lymphocytes in accordance with the elevated expression of sPLA2-IB and TNF-alpha mRNAs during endotoxic shock. In addition, the elevated expression level of TNF-alpha transcript was significantly reduced by the deficiency of PLA2R, suggesting that PLA2R plays a role in the regulation of TNF-alpha expression in these cell types. We then synthesized a specific sPLA2 inhibitor, indoxam, which blocked the binding of sPLA2-IB and X to PLA2R. Indoxam was found to suppress the elevation of the plasma level of TNF-alpha and prolonged the survival of endotoxin-challenged mice. The inhibitory effects of indoxam were abolished by the deficiency of PLA2R, demonstrating the involvement of PLA2R in the progression of endotoxic shock. We also detected and characterized a soluble form of PLA2R protein in the plasma of mouse with anti-PLA2R antibody, and showed its potential role as an endogenous sPLA2 inhibitor. Taken together, a series of studies with PLA2R-knockout mice have elucidated a critical role of PLA2R in the regulation of the development of endotoxic shock.
pubmed:language
jpn
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Carbamates, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Group II Phospholipases A2, http://linkedlifedata.com/resource/pubmed/chemical/Group X Phospholipases A2, http://linkedlifedata.com/resource/pubmed/chemical/Indolizines, http://linkedlifedata.com/resource/pubmed/chemical/PLA2G10 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PLA2R1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2, http://linkedlifedata.com/resource/pubmed/chemical/Pla2g10 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Pla2r1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Phospholipase A2, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/indoxam
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0031-6903
pubmed:author
pubmed:issnType
Print
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-33
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
[Functional analysis of phospholipase A2 receptor by gene knockout studies].
pubmed:affiliation
Shionogi Research Laboratories, Shionogi & Co., Ltd., 5-12-4, Sagisu, Fukushima-ku, Osaka 553-0002, Japan.
pubmed:publicationType
Journal Article, English Abstract, Review