TY - JOUR
T1 - Differential regulation of fatty acid amide hydrolase promoter in human immune cells and neuronal cells by leptin and progesterone
AU - Maccarrone, Mauro
AU - Gasperi, Valeria
AU - Fezza, Filomena
AU - Finazzi-Agrò, Alessandro
AU - Rossi, Antonello
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
KW - Endocannabinoids
KW - Immune system
KW - Leptin
KW - Neurons
KW - Progesterone
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U2 - 10.1111/j.1432-1033.2004.04427.x
DO - 10.1111/j.1432-1033.2004.04427.x
M3 - Article
C2 - 15606754
AN - SCOPUS:11244306367
VL - 271
SP - 4666
EP - 4676
JO - European Journal of Biochemistry
JF - European Journal of Biochemistry
SN - 0014-2956
IS - 23-24
ER -