10-Hydroxydecanoic acid inhibits LPS-induced inflammation by targeting p53 in microglial cells.

Abstract

Neuroinflammation, characterized by the activation of microglia and astrocytes, is important in the pathogenesis of many neurological disorders, such as Alzheimer's disease. Nonsteroidal anti-inflammatory drugs (NSAIDs), a group of chemically heterogenous medications, are used widely in the treatment of inflammation. However, the safety of these drugs is a growing concern due to their side effects on the gastrointestinal tract and liver. Royal jelly (RJ) is a potential functional food produced by the hypopharynx and mandibular salivary glands of nurse bees. In this study, we explored the anti-neuroinflammatory effect of 10-hydroxydecanoic acid (10-HDAA), which is the second most abundant but less studied fatty acid in RJ. We showed that 10-HDAA decreased the lipopolysaccharide (LPS)-induced elevation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) levels in both microglial BV-2 and N9 cell lines. Compared to the LPS group, the 10-HDAA/LPS treated BV-2 cells had a higher level of the phagocytic receptor TREM2. RNAseq transcriptomic results showed a different transcriptional profile between the LPS group and the 10-HDAA/LPS group in BV-2 cells and the 10-HDAA pre-treatment significantly decreased levels of pro-inflammatory mediators, which were further confirmed by qRT-PCR analysis. Moreover, we found that p53 was a target of 10-HDAA. p53 may mediate the anti-inflammation effect of 10-HDAA in two ways: first by directly deactivating the NLRP3 inflammatory pathway, second by indirectly promoting autophagy. Taken together, our results reveal a novel function of tumor suppressor p53 in the inhibition of neuroinflammation and provide a theoretical basis for broadening the application range of 10-HDAA and RJ.

• Authors: Mengmeng You, Zhuoning Miao, Olimpia Sienkiewicz, Xiasen Jiang, Xin Zhao, Fuliang Hu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 84 Pg. 106501 (Jul 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32311670 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• 10-hydroxydecanoic acid
• Anti-Inflammatory Agents, Non-Steroidal
• Decanoic Acids
• Fatty Acids
• Inflammation Mediators
• Lipopolysaccharides
• NLR Family, Pyrin Domain-Containing 3 Protein
• Tumor Suppressor Protein p53
• Nitric Oxide
• Nitric Oxide Synthase Type II
• royal jelly

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Autophagy (drug effects)
• Cell Line
• Decanoic Acids (pharmacology)
• Fatty Acids (chemistry, pharmacology)
• Inflammation (chemically induced, drug therapy)
• Inflammation Mediators (metabolism)
• Lipopolysaccharides (pharmacology)
• Mice
• Microglia (drug effects, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Signal Transduction (drug effects)
• Transcriptome (drug effects)
• Tumor Suppressor Protein p53 (drug effects, metabolism)