Differential regulation of fatty acid amide hydrolase promoter in human immune cells and neuronal cells by leptin and progesterone

Mauro Maccarrone, Valeria Gasperi, Filomena Fezza, Alessandro Finazzi-Agrò, Antonello Rossi

Research output: Contribution to journalArticlepeer-review

Abstract

We have shown recently that in human T lymphocytes, leptin stimulates activity and expression of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH), through STAT3 (signal transducer and activator of transcription 3) and its CRE (cAMP response element)-like transcriptional target in the FAAH promoter [Maccarrone, M., Di Rienzo, M., Finazzi-Agrò, A., & Rossi, A. (2003) J. Biol. Chem. 278, 13318-13324]. We have also shown that progesterone, alone or additively with leptin, up-regulates the FAAH gene in human T-cells, through the Ikaros transcription factor [Maccarrone, M., Bari, M., Di Rienzo, M., Finazzi-Agrò, A., & Rossi, A. (2003) J. Biol. Chem. 278, 32726-32732]. Here, we extend these observations to immortalized human lymphoma U937 cells, where stimulation of FAAH by leptin (up to ≈ 300% of the controls) involves binding to a leptin receptor (Kd = 2.0 ± 0.1 nM, Bmax = 382 ± 5 fmol·mg protein-1, apparent molecular mass of ≈ 110 kDa), and stimulation by progesterone involves an intracellular receptor of ≈ 120 kDa. Unlike FAAH, the other proteins of the endocannabinoid system are not modulated by the two hormones. Interestingly, human neuroblastoma CHP100 cells also have a leptin receptor (≈ 110 kDa, Kd = 2.2 ± 0.2 nM, Bmax = 339 ± 8 fmol·mg protein-1), a progesterone receptor (≈ 120 kDa), STAT3 and Ikaros, yet their FAAH is not activated by leptin or progesterone. These data, corroborated by transient expression and electrophoretic mobility-shift assays, demonstrate an unprecedented cell-specific regulation of the FAAH gene, which has important implications for the control of tone and activity of AEA along the neuroimmune axis.

Original languageEnglish
Pages (from-to)4666-4676
Number of pages11
JournalEuropean Journal of Biochemistry
Volume271
Issue number23-24
DOIs
Publication statusPublished - Dec 2004

Keywords

  • Endocannabinoids
  • Immune system
  • Leptin
  • Neurons
  • Progesterone

ASJC Scopus subject areas

  • Biochemistry

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