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

J Invest Dermatol. 2019 Apr;139(4):868-877. doi: 10.1016/j.jid.2018.10.021. Epub 2018 Oct 31.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alarmins / metabolism*
  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Calgranulin B / biosynthesis
  • Calgranulin B / drug effects
  • Calgranulin B / genetics
  • Cells, Cultured
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation*
  • Immunohistochemistry
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylglycerols / pharmacology*
  • Psoriasis / genetics*
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • RNA / genetics*
  • Signal Transduction
  • Toll-Like Receptors / biosynthesis
  • Toll-Like Receptors / genetics*


  • Alarmins
  • Calgranulin B
  • Phosphatidylglycerols
  • S100A9 protein, mouse
  • Toll-Like Receptors
  • RNA
  • 1,2-dioleoyl-sn-glycero-3-phosphoglycerol