Ultramicronized palmitoylethanolamide inhibits NLRP3 inflammasome expression and pro-inflammatory response activated by SARS-CoV-2 spike protein in cultured murine alveolar macrophages
| Autor: | Luisa Seguella, Giovanni Sarnelli, Giuseppe Esposito, Chiara Corpetti, Alessandro Del Re, Marcella Pesce, Irene Palenca, Barbara De Conno, Sara Rurgo, Luca Steardo |
|---|---|
| Přispěvatelé: | Del Re, A., Corpetti, C., Pesce, M., Seguella, L., Steardo, L., Palenca, I., Rurgo, S., De Conno, B., Sarnelli, G., Esposito, G. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
COVID19
Endocrinology Diabetes and Metabolism Murine alveolar macrophage Spike protein Biochemistry Microbiology Article Proinflammatory cytokine chemistry.chemical_compound Downregulation and upregulation NLRP3 medicine um-PEA murine alveolar macrophages spike protein Um-PEA Receptor Molecular Biology Palmitoylethanolamide food and beverages Inflammasome QR1-502 Cell biology chemistry Mechanism of action TLR4 Tumor necrosis factor alpha medicine.symptom medicine.drug |
| Zdroj: | Metabolites, Vol 11, Iss 592, p 592 (2021) Metabolites Volume 11 Issue 9 |
| Popis: | Despite its possible therapeutic potential against COVID-19, the exact mechanism(s) by which palmitoylethanolamide (PEA) exerts its beneficial activity is still unclear. PEA has demonstrated analgesic, anti-allergic, and anti-inflammatory activities. Most of the anti-inflammatory properties of PEA arise from its ability to antagonize nuclear factor-κB (NF-κB) signalling pathway via the selective activation of the PPARα receptors. Acting at this site, PEA can downstream several genes involved in the inflammatory response, including cytokines (TNF-α, Il-1β) and other signal mediators, such as inducible nitric oxide synthase (iNOS) and COX2. To shed light on this, we tested the anti-inflammatory and immunomodulatory activity of ultramicronized(um)-PEA, both alone and in the presence of specific peroxisome proliferator-activated receptor alpha (PPAR-α) antagonist MK886, in primary cultures of murine alveolar macrophages exposed to SARS-CoV-2 spike glycoprotein (SP). SP challenge caused a significant concentration-dependent increase in proinflammatory markers (TLR4, p-p38 MAPK, NF-κB) paralleled to a marked upregulation of inflammasome-dependent inflammatory pathways (NLRP3, Caspase-1) with IL-6, IL-1β, TNF-α over-release, compared to vehicle group. We also observed a significant concentration-dependent increase in angiotensin-converting enzyme-2 (ACE-2) following SP challenge. um-PEA concentration-dependently reduced all the analyzed proinflammatory markers fostering a parallel downregulation of ACE-2. Our data show for the first time that um-PEA, via PPAR-α, markedly inhibits the SP induced NLRP3 signalling pathway outlining a novel mechanism of action of this lipid against COVID-19. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|