Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns

Vivek Choudhary, Rawipan Uaratanawong, Ravi R. Patel, Hirel Patel, Wendi Bao, Bernadette Hartney, Elyssa Cohen, Xunsheng Chen, Qing Zhong, Carlos M. Isales, Wendy B. Bollag

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Psoriasis is a common skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes and inflammation. We previously showed that phosphatidylglycerol (PG) can regulate keratinocyte function and suppress skin inflammation. Based on data suggesting that PG can inhibit toll-like receptor (TLR) activation induced by microorganisms and their components, we determined whether PG can inhibit TLR activation in response to antimicrobial peptides. These peptides, which are up-regulated in psoriasis, are known to function as danger-associated molecular patterns (i.e., DAMPs) to activate TLRs and the innate immune system. Because S100A9 is elevated in psoriatic skin and in animal models of psoriasis, we selected S100A9 as a representative antimicrobial peptide DAMP. We showed that in primary keratinocytes and a macrophage cell line, PG suppressed inflammatory mediator production induced by recombinant S100A9 functioning through both TLR2 and TLR4. In addition, PG, but not phosphatidylcholine, inhibited downstream S100A9-elicited TLR2 and NF-κB activation. These results, to our knowledge previously unreported, show PG's ability to inhibit DAMP-induced TLR activation, thereby reducing inflammatory signals. In addition, topical PG ameliorated skin lesions and inflammation in a mouse model of psoriasis. Together, these results suggest the possibility of developing PG as a therapy for psoriasis.

Original languageEnglish (US)
Pages (from-to)868-877
Number of pages10
JournalJournal of Investigative Dermatology
Volume139
Issue number4
DOIs
StatePublished - Apr 2019

Fingerprint

Phosphatidylglycerols
Psoriasis
Inflammation
Toll-Like Receptors
Skin
Chemical activation
Keratinocytes
Peptides
Macrophages
Immune system
Phosphatidylcholines
Microorganisms
Immune System
Animals
Animal Models
Cells
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns. / Choudhary, Vivek; Uaratanawong, Rawipan; Patel, Ravi R.; Patel, Hirel; Bao, Wendi; Hartney, Bernadette; Cohen, Elyssa; Chen, Xunsheng; Zhong, Qing; Isales, Carlos M.; Bollag, Wendy B.

In: Journal of Investigative Dermatology, Vol. 139, No. 4, 04.2019, p. 868-877.

Research output: Contribution to journalArticle

Choudhary, Vivek ; Uaratanawong, Rawipan ; Patel, Ravi R. ; Patel, Hirel ; Bao, Wendi ; Hartney, Bernadette ; Cohen, Elyssa ; Chen, Xunsheng ; Zhong, Qing ; Isales, Carlos M. ; Bollag, Wendy B. / Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns. In: Journal of Investigative Dermatology. 2019 ; Vol. 139, No. 4. pp. 868-877.
@article{75078f0a06214e75817b1f9078ec2a58,
title = "Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns",
abstract = "Psoriasis is a common skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes and inflammation. We previously showed that phosphatidylglycerol (PG) can regulate keratinocyte function and suppress skin inflammation. Based on data suggesting that PG can inhibit toll-like receptor (TLR) activation induced by microorganisms and their components, we determined whether PG can inhibit TLR activation in response to antimicrobial peptides. These peptides, which are up-regulated in psoriasis, are known to function as danger-associated molecular patterns (i.e., DAMPs) to activate TLRs and the innate immune system. Because S100A9 is elevated in psoriatic skin and in animal models of psoriasis, we selected S100A9 as a representative antimicrobial peptide DAMP. We showed that in primary keratinocytes and a macrophage cell line, PG suppressed inflammatory mediator production induced by recombinant S100A9 functioning through both TLR2 and TLR4. In addition, PG, but not phosphatidylcholine, inhibited downstream S100A9-elicited TLR2 and NF-κB activation. These results, to our knowledge previously unreported, show PG's ability to inhibit DAMP-induced TLR activation, thereby reducing inflammatory signals. In addition, topical PG ameliorated skin lesions and inflammation in a mouse model of psoriasis. Together, these results suggest the possibility of developing PG as a therapy for psoriasis.",
author = "Vivek Choudhary and Rawipan Uaratanawong and Patel, {Ravi R.} and Hirel Patel and Wendi Bao and Bernadette Hartney and Elyssa Cohen and Xunsheng Chen and Qing Zhong and Isales, {Carlos M.} and Bollag, {Wendy B.}",
year = "2019",
month = "4",
doi = "10.1016/j.jid.2018.10.021",
language = "English (US)",
volume = "139",
pages = "868--877",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns

AU - Choudhary, Vivek

AU - Uaratanawong, Rawipan

AU - Patel, Ravi R.

AU - Patel, Hirel

AU - Bao, Wendi

AU - Hartney, Bernadette

AU - Cohen, Elyssa

AU - Chen, Xunsheng

AU - Zhong, Qing

AU - Isales, Carlos M.

AU - Bollag, Wendy B.

PY - 2019/4

Y1 - 2019/4

N2 - Psoriasis is a common skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes and inflammation. We previously showed that phosphatidylglycerol (PG) can regulate keratinocyte function and suppress skin inflammation. Based on data suggesting that PG can inhibit toll-like receptor (TLR) activation induced by microorganisms and their components, we determined whether PG can inhibit TLR activation in response to antimicrobial peptides. These peptides, which are up-regulated in psoriasis, are known to function as danger-associated molecular patterns (i.e., DAMPs) to activate TLRs and the innate immune system. Because S100A9 is elevated in psoriatic skin and in animal models of psoriasis, we selected S100A9 as a representative antimicrobial peptide DAMP. We showed that in primary keratinocytes and a macrophage cell line, PG suppressed inflammatory mediator production induced by recombinant S100A9 functioning through both TLR2 and TLR4. In addition, PG, but not phosphatidylcholine, inhibited downstream S100A9-elicited TLR2 and NF-κB activation. These results, to our knowledge previously unreported, show PG's ability to inhibit DAMP-induced TLR activation, thereby reducing inflammatory signals. In addition, topical PG ameliorated skin lesions and inflammation in a mouse model of psoriasis. Together, these results suggest the possibility of developing PG as a therapy for psoriasis.

AB - Psoriasis is a common skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes and inflammation. We previously showed that phosphatidylglycerol (PG) can regulate keratinocyte function and suppress skin inflammation. Based on data suggesting that PG can inhibit toll-like receptor (TLR) activation induced by microorganisms and their components, we determined whether PG can inhibit TLR activation in response to antimicrobial peptides. These peptides, which are up-regulated in psoriasis, are known to function as danger-associated molecular patterns (i.e., DAMPs) to activate TLRs and the innate immune system. Because S100A9 is elevated in psoriatic skin and in animal models of psoriasis, we selected S100A9 as a representative antimicrobial peptide DAMP. We showed that in primary keratinocytes and a macrophage cell line, PG suppressed inflammatory mediator production induced by recombinant S100A9 functioning through both TLR2 and TLR4. In addition, PG, but not phosphatidylcholine, inhibited downstream S100A9-elicited TLR2 and NF-κB activation. These results, to our knowledge previously unreported, show PG's ability to inhibit DAMP-induced TLR activation, thereby reducing inflammatory signals. In addition, topical PG ameliorated skin lesions and inflammation in a mouse model of psoriasis. Together, these results suggest the possibility of developing PG as a therapy for psoriasis.

UR - http://www.scopus.com/inward/record.url?scp=85059825248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059825248&partnerID=8YFLogxK

U2 - 10.1016/j.jid.2018.10.021

DO - 10.1016/j.jid.2018.10.021

M3 - Article

C2 - 30391260

AN - SCOPUS:85059825248

VL - 139

SP - 868

EP - 877

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 4

ER -