Rimonabant inhibits TNF-α-induced endothelial IL-6 secretion via CB1 receptor and cAMP-dependent protein kinase pathway

Nan Lan Huang, Jyh Ming Juang, Yi Ho Wang, Chia Hsiang Hsueh, Yao Jen Liang, Jiunn Lee Lin, Chia Ti Tsai, Ling Ping Lai

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aim: To investigate whether rimonabant, a cannabinoid receptor antagonist, had inhibitory effects on inflammatory reactions in human umbilical vein endothelial cells (HUVEC). Methods: TNF-α-induced IL-6 production was measured by ELISA and effects on related signaling pathways were investigated by immunoblot analysis. Cellular cAMP level was measured using kinase-coupled luciferase reaction. Results: Rimonabant at 1 and 10 mol/L significantly inhibited TNF-α-induced IL-6 production when added 15, 30 and 60 minutes before TNF-α treatment. Rimonabant also inhibited TNF-α-induced phosphorylation of IB kinase (IKK) α/β and IB-α degradation. ACEA, a cannabinoid receptor subtype 1 (CB1) agonist, added before rimonabant abolished the former effects of rimonabant. H-89, an inhibitor of cAMP-dependent protein kinase (PKA), abolished the inhibitory effects of rimonabant on TNF-α induced IL-6 production. Rimonabant also increased the phosphorylation of PKA regulatory subunit II (PKA-RII), implying the essential role of PKA activation in the inhibitory effects of rimonabant. Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin did not abolish the inhibitory effects of rimonabant on TNF-α induced IL-6 production. Conclusion: Rimonabant had anti-inflammatory effects on endothelial cells and inhibited TNF-α-induced IKKα/β phosphorylation, IB-α degradation and IL-6 production in HUVEC. This effect was related to CB1 antagonism and PKA activation.

Original languageEnglish
Pages (from-to)1447-1453
Number of pages7
JournalActa Pharmacologica Sinica
Volume31
Issue number11
DOIs
Publication statusPublished - Nov 1 2010
Externally publishedYes

Fingerprint

rimonabant
Cannabinoid Receptor CB1
Cyclic AMP-Dependent Protein Kinases
Interleukin-6
Protein Kinases
Human Umbilical Vein Endothelial Cells
Phosphorylation
Phosphotransferases
Phosphatidylinositol 3-Kinase
Cannabinoid Receptor Antagonists
Cannabinoid Receptors

Keywords

  • cAMP-dependent protein kinase
  • CB1 receptor
  • endothelial cells
  • inflammation
  • rimonabant

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Rimonabant inhibits TNF-α-induced endothelial IL-6 secretion via CB1 receptor and cAMP-dependent protein kinase pathway. / Huang, Nan Lan; Juang, Jyh Ming; Wang, Yi Ho; Hsueh, Chia Hsiang; Liang, Yao Jen; Lin, Jiunn Lee; Tsai, Chia Ti; Lai, Ling Ping.

In: Acta Pharmacologica Sinica, Vol. 31, No. 11, 01.11.2010, p. 1447-1453.

Research output: Contribution to journalArticle

Huang, Nan Lan ; Juang, Jyh Ming ; Wang, Yi Ho ; Hsueh, Chia Hsiang ; Liang, Yao Jen ; Lin, Jiunn Lee ; Tsai, Chia Ti ; Lai, Ling Ping. / Rimonabant inhibits TNF-α-induced endothelial IL-6 secretion via CB1 receptor and cAMP-dependent protein kinase pathway. In: Acta Pharmacologica Sinica. 2010 ; Vol. 31, No. 11. pp. 1447-1453.
@article{9652744fba394a118adc223e9cb2640b,
title = "Rimonabant inhibits TNF-α-induced endothelial IL-6 secretion via CB1 receptor and cAMP-dependent protein kinase pathway",
abstract = "Aim: To investigate whether rimonabant, a cannabinoid receptor antagonist, had inhibitory effects on inflammatory reactions in human umbilical vein endothelial cells (HUVEC). Methods: TNF-α-induced IL-6 production was measured by ELISA and effects on related signaling pathways were investigated by immunoblot analysis. Cellular cAMP level was measured using kinase-coupled luciferase reaction. Results: Rimonabant at 1 and 10 mol/L significantly inhibited TNF-α-induced IL-6 production when added 15, 30 and 60 minutes before TNF-α treatment. Rimonabant also inhibited TNF-α-induced phosphorylation of IB kinase (IKK) α/β and IB-α degradation. ACEA, a cannabinoid receptor subtype 1 (CB1) agonist, added before rimonabant abolished the former effects of rimonabant. H-89, an inhibitor of cAMP-dependent protein kinase (PKA), abolished the inhibitory effects of rimonabant on TNF-α induced IL-6 production. Rimonabant also increased the phosphorylation of PKA regulatory subunit II (PKA-RII), implying the essential role of PKA activation in the inhibitory effects of rimonabant. Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin did not abolish the inhibitory effects of rimonabant on TNF-α induced IL-6 production. Conclusion: Rimonabant had anti-inflammatory effects on endothelial cells and inhibited TNF-α-induced IKKα/β phosphorylation, IB-α degradation and IL-6 production in HUVEC. This effect was related to CB1 antagonism and PKA activation.",
keywords = "cAMP-dependent protein kinase, CB1 receptor, endothelial cells, inflammation, rimonabant",
author = "Huang, {Nan Lan} and Juang, {Jyh Ming} and Wang, {Yi Ho} and Hsueh, {Chia Hsiang} and Liang, {Yao Jen} and Lin, {Jiunn Lee} and Tsai, {Chia Ti} and Lai, {Ling Ping}",
year = "2010",
month = "11",
day = "1",
doi = "10.1038/aps.2010.126",
language = "English",
volume = "31",
pages = "1447--1453",
journal = "Acta Pharmacologica Sinica",
issn = "1671-4083",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Rimonabant inhibits TNF-α-induced endothelial IL-6 secretion via CB1 receptor and cAMP-dependent protein kinase pathway

AU - Huang, Nan Lan

AU - Juang, Jyh Ming

AU - Wang, Yi Ho

AU - Hsueh, Chia Hsiang

AU - Liang, Yao Jen

AU - Lin, Jiunn Lee

AU - Tsai, Chia Ti

AU - Lai, Ling Ping

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Aim: To investigate whether rimonabant, a cannabinoid receptor antagonist, had inhibitory effects on inflammatory reactions in human umbilical vein endothelial cells (HUVEC). Methods: TNF-α-induced IL-6 production was measured by ELISA and effects on related signaling pathways were investigated by immunoblot analysis. Cellular cAMP level was measured using kinase-coupled luciferase reaction. Results: Rimonabant at 1 and 10 mol/L significantly inhibited TNF-α-induced IL-6 production when added 15, 30 and 60 minutes before TNF-α treatment. Rimonabant also inhibited TNF-α-induced phosphorylation of IB kinase (IKK) α/β and IB-α degradation. ACEA, a cannabinoid receptor subtype 1 (CB1) agonist, added before rimonabant abolished the former effects of rimonabant. H-89, an inhibitor of cAMP-dependent protein kinase (PKA), abolished the inhibitory effects of rimonabant on TNF-α induced IL-6 production. Rimonabant also increased the phosphorylation of PKA regulatory subunit II (PKA-RII), implying the essential role of PKA activation in the inhibitory effects of rimonabant. Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin did not abolish the inhibitory effects of rimonabant on TNF-α induced IL-6 production. Conclusion: Rimonabant had anti-inflammatory effects on endothelial cells and inhibited TNF-α-induced IKKα/β phosphorylation, IB-α degradation and IL-6 production in HUVEC. This effect was related to CB1 antagonism and PKA activation.

AB - Aim: To investigate whether rimonabant, a cannabinoid receptor antagonist, had inhibitory effects on inflammatory reactions in human umbilical vein endothelial cells (HUVEC). Methods: TNF-α-induced IL-6 production was measured by ELISA and effects on related signaling pathways were investigated by immunoblot analysis. Cellular cAMP level was measured using kinase-coupled luciferase reaction. Results: Rimonabant at 1 and 10 mol/L significantly inhibited TNF-α-induced IL-6 production when added 15, 30 and 60 minutes before TNF-α treatment. Rimonabant also inhibited TNF-α-induced phosphorylation of IB kinase (IKK) α/β and IB-α degradation. ACEA, a cannabinoid receptor subtype 1 (CB1) agonist, added before rimonabant abolished the former effects of rimonabant. H-89, an inhibitor of cAMP-dependent protein kinase (PKA), abolished the inhibitory effects of rimonabant on TNF-α induced IL-6 production. Rimonabant also increased the phosphorylation of PKA regulatory subunit II (PKA-RII), implying the essential role of PKA activation in the inhibitory effects of rimonabant. Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin did not abolish the inhibitory effects of rimonabant on TNF-α induced IL-6 production. Conclusion: Rimonabant had anti-inflammatory effects on endothelial cells and inhibited TNF-α-induced IKKα/β phosphorylation, IB-α degradation and IL-6 production in HUVEC. This effect was related to CB1 antagonism and PKA activation.

KW - cAMP-dependent protein kinase

KW - CB1 receptor

KW - endothelial cells

KW - inflammation

KW - rimonabant

UR - http://www.scopus.com/inward/record.url?scp=78149379077&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149379077&partnerID=8YFLogxK

U2 - 10.1038/aps.2010.126

DO - 10.1038/aps.2010.126

M3 - Article

VL - 31

SP - 1447

EP - 1453

JO - Acta Pharmacologica Sinica

JF - Acta Pharmacologica Sinica

SN - 1671-4083

IS - 11

ER -