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

M. Maccarrone, L. De Petrocellis, M. Bari, F. Fezza, S. Salvati, V. Di Marzo, A. Finazzi-Agrò

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Lipopolysaccharide (LPS) increases the levels of the endogenous cannabinoid anandamide (N-arachidonoylethanolamine, AEA) 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 AEA 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 AEA 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.

Original languageEnglish
Pages (from-to)321-328
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume393
Issue number2
DOIs
Publication statusPublished - Sep 15 2001

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Lymphocytes
Lipopolysaccharides
Down-Regulation
Endocannabinoids
Cannabinoid Receptor CB1
Cannabinoid Receptors
Cannabinoids
Macrophages
fatty-acid amide hydrolase
N-arachidonoylethanolamine
anandamide
Gene expression
Endotoxins
Rats
Homeostasis
Chemical activation
Gene Expression
Enzymes

Keywords

  • Anandamide
  • Endotoxic shock
  • Human
  • Lipid mediators
  • Lymphocytes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Lipopolysaccharide downregulates fatty acid amide hydrolase expression and increases anandamide levels in human peripheral lymphocytes. / Maccarrone, M.; De Petrocellis, L.; Bari, M.; Fezza, F.; Salvati, S.; Di Marzo, V.; Finazzi-Agrò, A.

In: Archives of Biochemistry and Biophysics, Vol. 393, No. 2, 15.09.2001, p. 321-328.

Research output: Contribution to journalArticle

Maccarrone, M. ; De Petrocellis, L. ; Bari, M. ; Fezza, F. ; Salvati, S. ; Di Marzo, V. ; Finazzi-Agrò, A. / Lipopolysaccharide downregulates fatty acid amide hydrolase expression and increases anandamide levels in human peripheral lymphocytes. In: Archives of Biochemistry and Biophysics. 2001 ; Vol. 393, No. 2. pp. 321-328.
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