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

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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.

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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

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Correspondence to Xiao-Feng Yang.

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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.

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

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Associate Editor Angela Taylor oversaw the review of this article

Ya-Feng Li, Gayani Nanayakkara, Ying Shao and Bin Liang contributed equally to this work.

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Wang, X., Li, YF., Nanayakkara, G. et al. Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation—Novel Paradigm and Therapeutic Potential. J. of Cardiovasc. Trans. Res. 9, 343–359 (2016). https://doi.org/10.1007/s12265-016-9700-6

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  • DOI: https://doi.org/10.1007/s12265-016-9700-6

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