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Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation-Novel Paradigm and Therapeutic Potential.

Abstract
There are limitations in the current classification of danger-associated molecular patterns (DAMP) receptors. To overcome these limitations, we propose a new paradigm by using endogenous metabolites lysophospholipids (LPLs) as a prototype. By utilizing a data mining method we pioneered, we made the following findings: (1) endogenous metabolites such as LPLs at basal level have physiological functions; (2) under sterile inflammation, expression of some LPLs is elevated. These LPLs act as conditional DAMPs or anti-inflammatory homeostasis-associated molecular pattern molecules (HAMPs) for regulating the progression of inflammation or inhibition of inflammation, respectively; (3) receptors for conditional DAMPs and HAMPs are differentially expressed in human and mouse tissues; and (4) complex signaling mechanism exists between pro-inflammatory mediators and classical DAMPs that regulate the expression of conditional DAMPs and HAMPs. This novel insight will facilitate identification of novel conditional DAMPs and HAMPs, thus promote development of new therapeutic targets to treat inflammatory disorders.
AuthorsXin Wang, Ya-Feng Li, Gayani Nanayakkara, Ying Shao, Bin Liang, Lauren Cole, William Y Yang, Xinyuan Li, Ramon Cueto, Jun Yu, Hong Wang, Xiao-Feng Yang
JournalJournal of cardiovascular translational research (J Cardiovasc Transl Res) Vol. 9 Issue 4 Pg. 343-59 (08 2016) ISSN: 1937-5395 [Electronic] United States
PMID27230673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
Chemical References
  • Lysophospholipids
  • Receptors, Lysophospholipid
Topics
  • Animals
  • Computational Biology
  • Data Mining
  • Databases, Genetic
  • Disease Models, Animal
  • Gene Expression Profiling (methods)
  • Homeostasis
  • Humans
  • Inflammation (immunology, metabolism)
  • Lysophospholipids (immunology, metabolism)
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Protein Binding
  • Receptors, Lysophospholipid (genetics, immunology, metabolism)
  • Signal Transduction

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