Format

Send to

Choose Destination
J Invest Dermatol. 2018 Oct 31. pii: S0022-202X(18)32774-X. doi: 10.1016/j.jid.2018.10.021. [Epub ahead of print]

Phosphatidylglycerol inhibits toll-like receptor-mediated inflammation by danger-associated molecular patterns.

Author information

1
Charlie Norwood VA Medical Center, Augusta, GA 30904; Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912.
2
Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912; Department of Medicine (Dermatology), Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, 10300, Thailand.
3
Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912.
4
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912.
5
Charlie Norwood VA Medical Center, Augusta, GA 30904; Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912. Electronic address: wbollag@augusta.edu.

Abstract

Psoriasis is a common skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes and inflammation. We previously demonstrated 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 anti-microbial peptides. These peptides, which are up-regulated in psoriasis, are known to function as danger-associated molecular patterns (DAMPs) to activate TLRs and the innate immune system. Since S100A9 is elevated in psoriatic skin and in animal models of psoriasis, we selected S100A9 as a representative anti-microbial peptide DAMP. In exciting results we show 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 nuclear factor-κB activation. These results, to our knowledge previously unreported, demonstrate 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.

PMID:
30391260
DOI:
10.1016/j.jid.2018.10.021

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center