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

  • Xin 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
Original Article


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.


Lysophospholipid receptor Rheumatoid arthritis Atherosclerosis Danger-associated molecular pattern molecules receptor Homeostasis-associated molecular pattern molecules receptor 



Pathogen-associated molecular patterns


Danger-associated molecular patterns


Toll-like receptors


NOD-like receptors


Nucleotide binding and oligomerization domain


Retinoid acid inducible gene I


Absent in melanoma 2


Receptor for advanced glycation end product


High mobility group box 1




Transforming growth factor-β




G-protein coupled receptors


Lysophosphatidic acid












Coronary artery disease


Specialized pro-resolving mediators


Expressed sequence tags


National Institute of Health


National Center of Biotechnology Information


Rho-associated kinase




Inositol 1,4,5-triphosphate


Mitogen-activated protein kinase


Adenylate cyclase




Protein kinase C


Serum response factor






Compliance with Ethical Standards


This work was partially supported by the National Institutes of Health Grants to XFY, HW, and JY, and the American Heart Association Postdoctoral Fellowship to Dr. YFL.



Ethics Statement

N/A. This study only employed a data mining strategy and did not involve human participants or experimental animal models.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Xin Wang
    • 1
    • 2
  • Ya-Feng Li
    • 2
  • Gayani Nanayakkara
    • 2
  • Ying Shao
    • 2
  • Bin Liang
    • 1
  • Lauren Cole
    • 2
  • William Y. Yang
    • 2
  • Xinyuan Li
    • 2
  • Ramon Cueto
    • 2
  • Jun Yu
    • 2
  • Hong Wang
    • 2
  • Xiao-Feng Yang
    • 2
  1. 1.Department of MedicineThe Second Hospital of Shanxi Medical UniversityTaiyuanChina
  2. 2.Centers for Metabolic Disease Research, Cardiovascular Research & Thrombosis Research, Department of Pharmacology, Lewis Katz School of MedicineTemple UniversityPhiladelphiaUSA

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