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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

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.

Keywords

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

Abbreviations

PAMP

Pathogen-associated molecular patterns

DAMP

Danger-associated molecular patterns

TLR

Toll-like receptors

NLR

NOD-like receptors

NOD

Nucleotide binding and oligomerization domain

RIG-I

Retinoid acid inducible gene I

AIM2

Absent in melanoma 2

RAGE

Receptor for advanced glycation end product

HMGB1

High mobility group box 1

IL

Interleukin

TGF-β

Transforming growth factor-β

LPLs

Lysophospholipids

GPCRs

G-protein coupled receptors

LPA

Lysophosphatidic acid

LPC

Lysophosphatidylcholine

LPE

Lysophosphatidylenthaolamine

LPG

Lysophosphoglycan

LPI

Lysophosphatidylinositol

LysoPS

Lysophosphatidylserine

CAD

Coronary artery disease

SPM

Specialized pro-resolving mediators

EST

Expressed sequence tags

NIH

National Institute of Health

NCBI

National Center of Biotechnology Information

ROCK

Rho-associated kinase

DAG

Diacylglycerol

IP3

Inositol 1,4,5-triphosphate

MAPK

Mitogen-activated protein kinase

AC

Adenylate cyclase

PI3K

Phosphoinositide-3-kinase

PKC

Protein kinase C

SRF

Serum response factor

SPC

Sphingosylphosphorylcholine

IFN-γ

Interferon-γ

Notes

Compliance with Ethical Standards

Funding

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.

Disclosures

None

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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