Lipopolysaccharide (LPS) increases the levels of the endogenous cannabinoid anandamide (N-arachidonoylethanolamine, AFA) in rat macrophages, but the mechanism responsible for this effect has not been elucidated. Here we demonstrate that LPS enhances the levels of AEA (fourfold over controls) also in human lymphocytes. We show that in these cells LPS inhibits the activity of the AEA-degrading enzyme fatty acid amide hydrolase (FAAH), by downregulating the gene expression at transcriptional level. Lymphocytes have also a specific ARA transporter and a functional CB1 cannabinoid receptor, which were not modulated by LPS. The effect of this endotoxin on FAAH was not mediated by AEA-induced activation of cannabinoid receptors. Conversely, the stimulatory action of LPS on AEA levels might be due to inhibition of FAAH, as suggested by the observation that an increase of AFA amounts was also induced by an irreversible FAAH inhibitor. These results suggest that lymphocytes take part in regulating the peripheral endocannabinoid system and endocannabinoid homeostasis. (C) 2001 Academic Press.

Lipopolysaccharide downregulates fatty acid amide hydrolase expression and increases anandamide levels in human peripheral lymphocytes

Maccarrone M;
2001

Abstract

Lipopolysaccharide (LPS) increases the levels of the endogenous cannabinoid anandamide (N-arachidonoylethanolamine, AFA) in rat macrophages, but the mechanism responsible for this effect has not been elucidated. Here we demonstrate that LPS enhances the levels of AEA (fourfold over controls) also in human lymphocytes. We show that in these cells LPS inhibits the activity of the AEA-degrading enzyme fatty acid amide hydrolase (FAAH), by downregulating the gene expression at transcriptional level. Lymphocytes have also a specific ARA transporter and a functional CB1 cannabinoid receptor, which were not modulated by LPS. The effect of this endotoxin on FAAH was not mediated by AEA-induced activation of cannabinoid receptors. Conversely, the stimulatory action of LPS on AEA levels might be due to inhibition of FAAH, as suggested by the observation that an increase of AFA amounts was also induced by an irreversible FAAH inhibitor. These results suggest that lymphocytes take part in regulating the peripheral endocannabinoid system and endocannabinoid homeostasis. (C) 2001 Academic Press.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11697/155891
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 141
  • ???jsp.display-item.citation.isi??? 132
social impact