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

  • Int Immunopharmacol. 2020 Jul:84:106501. doi: 10.1016/j.intimp.2020.106501.
Mengmeng You  1 ,  Zhuoning Miao  2 ,  Olimpia Sienkiewicz  3 ,  Xiasen Jiang  2 ,  Xin Zhao  4 ,  Fuliang Hu  5
Affiliations
  • 1. College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; Department of Animal Science, McGill University, 21, 111 Lakeshore Road, Sainte-Anne-de-Bellevue H9X3V9, Quebec, Canada.
  • 2. College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
  • 3. Department of Animal Science, McGill University, 21, 111 Lakeshore Road, Sainte-Anne-de-Bellevue H9X3V9, Quebec, Canada.
  • 4. Department of Animal Science, McGill University, 21, 111 Lakeshore Road, Sainte-Anne-de-Bellevue H9X3V9, Quebec, Canada. Electronic address: [email protected].
  • 5. College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: [email protected].
PMID: 32311670 DOI: 10.1016/j.intimp.2020.106501
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.

Keywords
10-hydroxydecanoic acid; Autophagy; NLRP3 inflammasome; Neuroinflammation; P53.
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