Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways

Yang, Lichao; Guo, Hong-Fen; Li, Ying; Meng, Xianglan; Lü, Yan; Zhang, Dan; Wu, San‐Gang; Zhou, Hai-Rong; Lu, Peng; Xie, Qiang; Jin, Xin

doi:10.1038/srep34611

Cited by 79 publications

(81 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, on Day 2 there is a negative correlation between AEA and CD8+ T cells, implying heightening of immune response post vaccination (40) (40, 41). Similarly, an increase in the abundance of OEA occurs with a decrease in the pro-inflammatory IL-6 cytokine on Day 7, is in line with prior studies and suggesting the resolution of inflammation(42, 43) (39, 43). While no associations were identified between DA lipid responses and tularemia-specific microagglutination titer, CD4+ T-cell activation was linked to DA lipids at Day 1 while CD8 T-cell activation was associated with DA lipid changes at Days 2, 7, and 14.…”

Section: Discussionsupporting

confidence: 89%

Alterations in the human plasma lipidome in response to Tularemia vaccination

Maner-Smith

Ford

Goll

et al. 2020

Preprint

View full text Add to dashboard Cite

31Tularemia is a rare but highly contagious and potentially fatal disease caused by bacteria 32 Francisella tularensis where as few as ten inhaled organisms can lead to an infection, making it 33 one of the most infectious microorganisms known and a potential bioweapon. To better 34 understand the response to a live, attenuated tularemia vaccine and the biological pathways 35 altered post-vaccination, healthy adults were vaccinated by scarification and plasma was 36 collected pre-and post-vaccination for longitudinal lipidomics studies. Using tandem mass 37 spectrometry, we identified and quantified individual lipid molecular species within 38 representative lipid classes in plasma to characterize alterations in the plasma lipidome during 39 the vaccine response. Separately, we targeted oxylipins, a subset of lipid mediators involved in 40 inflammatory pathways. We identified 14 differentially abundant lipid species from eight lipid 41 classes. These included 5-Hydroxyeicosatetraenoic acid (5-HETE), an eicosanoid produced 42 following arachidonic acid liberation and epoxygenation, which is indicative of lipoxygenase 43 activity and, subsequently, inflammation. Results suggest that 5-HETE was metabolized to a 44 dihydroxyeicosatrienoic acid (DHET) by Day 7 post-vaccination, shedding light on the kinetics 45 of the 5-HETE-mediated inflammatory response. In addition to 5-HETE and DHET, we 46 observed pronounced changes in 34:1 phosphatidylinositol, anandamide, oleamide, ceramides, 47 16:1 cholesteryl ester, and several glycerophospholipids, several of these changes in abundance 48 were correlated with serum cytokines and T cell activation. These data provide new insights into 49 alterations in plasma lipidome post tularemia vaccination, potentially identifying key mediators 50 and pathways involved in vaccine response and efficacy. 51 52 53Vaccines initially trigger innate immune responses that result in development of an adaptive 54 immune response with establishment of immunological memory (1). This process is 55 incompletely understood but is probably best detailed for the Yellow Fever vaccine (2). This 56 vaccine is highly effective and elicits a wide range of immune responses, resulting in greater than 57 30 years of protection from yellow fever. Previously published research has shown that the 58 vaccine produces a biologic signature identified by transcriptomics, cytokine analyses and flow 59 cytometry (3). Such biologic signatures may correlate with immunogenicity to predict the 60 efficacy of novel vaccines. Lipids are key stress-response and immune signaling molecules and 61 changes in their circulating concentrations reflect a host of immune processes(4) (5) (6). Thus, 62 lipids play a critical role in inflammation. Accordingly, performing lipidomics analysis is a key 63 element in the systems-wide multi-omic platform approaches leveraging data from 64 transcriptomics, metabolomics, and proteomics to obtain a comprehensive picture of the vaccine 65 response. 67Tularemia, caused by the intracellular ...

show abstract

Section: Discussionsupporting

confidence: 89%

Alterations in the human plasma lipidome in response to Tularemia vaccination

Maner-Smith

Ford

Goll

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…OEA, a high affinity endogenous ligand of PPAR-α (28), binds to PPAR-α receptors, and increases the expression level of anti-inflammatory cytokine such as IL-10. In addition, it attenuates the inflammatory responses and decreases the expression of TLR4, and interfering with the ERK1/2/AP-1/STAT3 signaling cascade (29)(30)(31). In a recent clinical trial, OEA supplementation could decrease inflammation in obese patients via reducing serum concentrations of inflammatory markers including IL-6 and TNF-α (32).…”

Section: Oleoylethanolamide and Sars-cov-2 Infectionmentioning

confidence: 99%

Oleoylethanolamide, A Bioactive Lipid Amide, as A Promising Treatment Strategy for Coronavirus/COVID-19

Ghaffari

Roshanravan

Ostadrahimi

et al. 2020

Archives of Medical Research

View full text Add to dashboard Cite

E20_423 2 (WHO) as a global pandemic. With the emergence of the COVID-19 virus and considering the lack of effective pharmaceutical treatment for it, there is an urgent need to identify safe and effective drugs or potential adjuvant therapy in this regard. Bioactive lipids with an array of known healthpromoting properties can be suggested as effective agents in alleviating acute respiratory stress induced by virus. The bioactive lipid amide, oleoylethanolamide (OEA), due to several distinctive homeostatic properties, including anti-inflammatory activities, modulation of immune response, and anti-oxidant effects can be considered as a novel potential pharmacological alternative for the management of COVID-19.

show abstract

“…Yet, it was the seminal work of the late Nobel laureate Rita Levi Montalcini that rekindled interest in this molecule in the early 1990s, helping to unravel its potent anti-inflammatory and antinociceptive effects (5)(6)(7)(8). OEA and SEA mainly control food intake, metabolic pathways, and energy homeostasis (9,10); however, emerging evidence suggests that they might also control specific inflammatory cascades (11,12), adding a new dimension to their ability to affect metabolism. A number of additional NAEs have been detected in biological tissues [e.g., ETEA (13)], while others have been synthesized from different fatty acids, but their presence in vivo and biologic activity remain to be investigated.…”

mentioning

confidence: 99%

Bioactive lipids ALIAmides differentially modulate inflammatory responses of distinct subsets of primary human T lymphocytes

et al. 2018

View full text Add to dashboard Cite

Autacoid local injury antagonist amides (ALIAmides) are a family of endogenous bioactive acyl ethanolamides that include the renowned palmitoyl ethanolamide (PEA), oleoyl ethanolamide (OEA), and stearoyl ethanolamide (SEA), and that are involved in several biologic processes such as nociception, lipid metabolism, and inflammation. The role of ALIAmides in the control of inflammatory processes has recently gained much attention and prompted the use of these molecules or their analogs, and the pharmacologic manipulation of their endogenous levels, as plausible therapeutic strategies in the treatment of several chronic inflammatory conditions. Since chronic inflammation is mainly driven by cells of adaptive immunity, particularly T lymphocytes, we aimed at investigating whether such bioactive lipids could directly modulate T-cell responses. We found that OEA, PEA, and eicosatrienoyl ethanolamide (ETEA) could directly inhibit both T-cell responses by reducing their production of TNF-α and IFN-γ from CD8 T cells and TNF-α, IFN-γ and IL-17 from CD4 T cells. Furthermore, neither SEA nor docosatrienoyl ethanolamide (DTEA) could affect cytokine production from both T cell subsets. Interestingly, unlike OEA and ETEA, PEA was also able to enhance de novo generation of forkhead box P3 (FoxP3)-expressing regulatory T cells from CD4-naive T cells. Our findings show for the first time that specific ALIAmides can directly affect different T-cell subsets, and provide proof of their anti-inflammatory role in chronic inflammation, ultimately suggesting that these bioactive lipids could offer novel tools for the management of T-cell dependent chronic inflammatory diseases.-Chiurchiù, V., Leuti, A., Smoum, R., Mechoulam, R., Maccarrone, M. Bioactive lipids ALIAmides differentially modulate inflammatory responses of distinct subsets of primary human T lymphocytes.

show abstract

Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways

Cited by 79 publications

References 36 publications

Alterations in the human plasma lipidome in response to Tularemia vaccination

Alterations in the human plasma lipidome in response to Tularemia vaccination

Oleoylethanolamide, A Bioactive Lipid Amide, as A Promising Treatment Strategy for Coronavirus/COVID-19

Bioactive lipids ALIAmides differentially modulate inflammatory responses of distinct subsets of primary human T lymphocytes

Contact Info

Product

Resources

About