Pathogen-Associated Molecular Pattern-Induced TLR2 and TLR4 Activation Increases Keratinocyte Production of Inflammatory Mediators and is Inhibited by Phosphatidylglycerol
| Autor: | Vivek Choudhary, Xunsheng Chen, Wendy B. Bollag, Shantelle Griffith |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Keratinocytes Lipopolysaccharides Lipopolysaccharide Inflammation Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound Lipopeptides Mice 0302 clinical medicine medicine Animals Calgranulin B Humans Pharmacology Innate immune system Chemistry Pathogen-associated molecular pattern Macrophages Pathogen-Associated Molecular Pattern Molecules Imidazoles NF-kappa B Phosphatidylglycerols Articles Recombinant Proteins Toll-Like Receptor 2 Cell biology Toll-Like Receptor 4 TLR2 030104 developmental biology medicine.anatomical_structure RAW 264.7 Cells Receptors Pattern Recognition TLR4 Molecular Medicine Soybeans medicine.symptom Inflammation Mediators Erratum Keratinocyte 030217 neurology & neurosurgery |
| Zdroj: | Mol Pharmacol |
| ISSN: | 1521-0111 |
| Popis: | Skin serves not only as a protective barrier to microbial entry into the body but also as an immune organ. The outer layer, the epidermis, is composed predominantly of keratinocytes, which can be stimulated to produce proinflammatory mediators. Although some inflammation is useful to defend against infection, excessive or persistent inflammation can lead to the development of inflammatory skin diseases, such as psoriasis, a common skin disorder affecting approximately 2% of the US population. We have previously found that phosphatidylglycerol (PG) derived from soy can inhibit inflammation in a contact irritant ear edema mouse model. Here, we investigated the ability of soy PG to inhibit inflammatory mediator expression in response to activators of the pattern recognition receptors, toll-like receptor-2 (TLR2) and -4 (TLR4). We found that in epidermal keratinocytes, soy PG inhibited TLR2 and TLR4 activation and inflammatory mediator expression in response to a synthetic triacylated lipopeptide and lipopolysaccharide, respectively, as well as an endogenous danger-associated molecular pattern. However, at higher concentrations, soy PG alone enhanced the expression of some proinflammatory cytokines, suggesting a narrow therapeutic window for this lipid. Dioleoylphosphatidylglycerol (DOPG), but not dioleoylphosphatidylcholine, exerted a similar inhibitory effect, completely blocking keratinocyte inflammatory mediator expression induced by TLR2 and TLR4 activators as well as NFκB activation in a macrophage cell line (RAW264.7); however, DOPG was not itself proinflammatory even at high concentrations. Furthermore, DOPG had no effect on NFκB activation in response to a TLR7/8 agonist. Our results suggest that DOPG could be used to inhibit excessive skin inflammation. SIGNIFICANCE STATEMENT: Although inflammation is beneficial for clearing an infection, in some cases, the infection can be excessive and/or become chronic, thereby resulting in considerable tissue damage and pathological conditions. We show here that the phospholipid phosphatidylglycerol can inhibit the activation of toll-like receptors 2 and 4 of the innate immune system as well as the downstream inflammatory mediator expression in response to microbial component-mimicking agents in epidermal keratinocytes that form the physical barrier of the skin. |
| Databáze: | OpenAIRE |
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