Immunomodulatory effect of oleoylethanolamide in dendritic cells via TRPV1/AMPK activation

• Published in: Journal of cellular physiology 2019-10, Vol.234 (10), p.18392-18407
• Main Authors: Yao, Enhui, Zhang, Guixiang, Huang, Jinhua, Yang, Xiazhen, Peng, Lu, Huang, Xuefeng, Luo, Xiaoxin, Ren, Jie, Huang, Rui, Yang, Lichao, Zhou, Yu, Zhuo, Rengong, Zhao, Yun, Jin, Xin
• Format: Article
• Language: English
• Subjects: AMP; AMP-Activated Protein Kinases - metabolism; Animals; Body weight; Bone marrow; Calcium; Calcium (intracellular); Calcium - metabolism; Calcium imaging; Capsaicin receptors; Cell activation; Cell adhesion & migration; Cell migration; Cell proliferation; Cell surface; Classical pathway; Cytokines; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Down-Regulation - drug effects; Endocannabinoids - pharmacology; Energy metabolism; Female; Flow cytometry; Immunologic Factors - pharmacology; Immunomodulation; Kinases; Lipids; Lipopolysaccharides; Lymphocytes; Lymphocytes B; Lymphocytes T; Markers; Maturation; Metabolism; Mice, Inbred C57BL; NF-kappa B - metabolism; Oleic acid; Oleic Acids - pharmacology; oleoylethanolamide (OEA); peroxisome proliferator‐activated receptor alpha (PPARa); Polymerase chain reaction; Protein kinase; Proteins; Signal Transduction - drug effects; Surface markers; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; transient receptor potential vanilloid‐1 (TRPV1); TRPV Cation Channels - metabolism
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28474

Oleoylethanolamide (OEA) is an endogenous lipid mediator involved in the control of feeding, body weight, and energy metabolism. However, whether OEA modulates maturation of dendritic cells (DCs) has never been addressed. Hence, we evaluated the effect of OEA on DCs maturation in bone marrow‐derived DCs (BMDCs) in four aspects: (a) Cell surface markers were determined using flow cytometric analysis; (b) cell mobile ability was testified with the transwell assay; (c) stimulation of T cells proliferation was performed in a coculture system; and (d) cytokine production was measured using polymerase chain reaction (PCR). The result showed that, in mature BMDCs induced by lipopolysaccharides (LPS), the OEA treatment decreased expressions of cell surface markers, reduced cell migration, diminished the proliferation of cocultured T cells, and regulated cytokine production of BMDCs, indicating the modulatory effect of OEA on DCs maturation. Furthermore, to explore the underlying mechanism of the immunomodulatory effect of OEA, we used antagonists of transient receptor potential vanilloid‐1 (TRPV1) and AMP‐activated protein kinase (AMPK), determined the protein expressions of TRPV1/AMPK and Toll‐like receptor 4 (TLR4)/nuclear factor‐kappa B (NF‐κB) using western blot, and measured the intracellular calcium concentration using calcium imaging. The result illustrated that OEA downregulated TLR4/NF‐κB, the classical pathway leading to DCs maturation induced by LPS, through the activation of TRPV1 and AMPK. Collectively, the present study suggests that OEA suppresses DCs maturation through the activation of TRPV1/AMPK. These findings increase our understanding of this endogenous lipid OEA. Our study illustrates that oleoylethanolamide (OEA), an endogenous lipid, modulates maturation of dendritic cells. In addition, the mechanism of OEA modulating maturation of dendritic cells is exemplified to be downregulating TLR4/NF‐κB through the activation of TRPV1/AMPK. The study is novel in investigating the effect and mechanism of OEA modulating maturation of dendritic cells.