Endocannabinergic modulation of interleukin-1β in mouse hippocampus under basal conditions and after in vivo systemic lipopolysaccharide stimulation

Cecília Csölle, B. Sperlágh

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective: Cannabinoids play an important role in the suppression of proinflammatory cytokine production in the periphery and brain. In this study, we explored whether endogenous activation of cannabinoid (CB) 1 receptors (CB1Rs) affects interleukin (IL)-1β levels in the mouse hippocampus under basal conditions and following stimulation with in vivo bacterial lipopolysaccharide (LPS, 250 μg/kg i.p.). Methods: IL-1β levels were determined in the hippocampi of wild-type (WT), CB1R-/- and P2X7 receptor (P2X7R)-/- mice using an ELISA kit. Results: Basal but not LPS-induced IL-1β levels were downregulated when CB1R function was abrogated by genetic deletion, suggesting that endocannabinoids contributed to basal IL-1β content in the mouse hippocampus. AM251 (3 mg/kg i.p.), an antagonist of CB1Rs, also inhibited basal IL-1β protein in WT but not in CB1R-/- mice. In the absence of P2X7R, LPS-induced IL-1β production was lower, while the inhibitory effect of CB1R antagonists on basal IL-1β was significantly attenuated. The LPS-induced elevation in IL-1β production was decreased in the presence of AM251 and AM281, with no significant difference between WT and P2X7R-/- mice. Conclusions: CB1Rs are responsible for the modulation of basal IL-1β levels in the hippocampus, while the effects of CB1 antagonists on systemic LPS-induced IL-1β concentrations are independent of CB1Rs.

Original languageEnglish
Pages (from-to)226-231
Number of pages6
JournalNeuroImmunoModulation
Volume18
Issue number4
DOIs
Publication statusPublished - Jun 2011

Fingerprint

Interleukin-1
Lipopolysaccharides
Hippocampus
Purinergic P2X7 Receptors
Cannabinoid Receptors
Endocannabinoids
Cannabinoids
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Cytokines
Brain

Keywords

  • Cannabinoids
  • CB1 receptor
  • Hippocampus
  • In vivo endotoxin treatment
  • Interleukin-1β
  • Lipopolysaccharides
  • P2X

ASJC Scopus subject areas

  • Endocrinology
  • Immunology
  • Endocrine and Autonomic Systems
  • Neurology

Cite this

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title = "Endocannabinergic modulation of interleukin-1β in mouse hippocampus under basal conditions and after in vivo systemic lipopolysaccharide stimulation",
abstract = "Objective: Cannabinoids play an important role in the suppression of proinflammatory cytokine production in the periphery and brain. In this study, we explored whether endogenous activation of cannabinoid (CB) 1 receptors (CB1Rs) affects interleukin (IL)-1β levels in the mouse hippocampus under basal conditions and following stimulation with in vivo bacterial lipopolysaccharide (LPS, 250 μg/kg i.p.). Methods: IL-1β levels were determined in the hippocampi of wild-type (WT), CB1R-/- and P2X7 receptor (P2X7R)-/- mice using an ELISA kit. Results: Basal but not LPS-induced IL-1β levels were downregulated when CB1R function was abrogated by genetic deletion, suggesting that endocannabinoids contributed to basal IL-1β content in the mouse hippocampus. AM251 (3 mg/kg i.p.), an antagonist of CB1Rs, also inhibited basal IL-1β protein in WT but not in CB1R-/- mice. In the absence of P2X7R, LPS-induced IL-1β production was lower, while the inhibitory effect of CB1R antagonists on basal IL-1β was significantly attenuated. The LPS-induced elevation in IL-1β production was decreased in the presence of AM251 and AM281, with no significant difference between WT and P2X7R-/- mice. Conclusions: CB1Rs are responsible for the modulation of basal IL-1β levels in the hippocampus, while the effects of CB1 antagonists on systemic LPS-induced IL-1β concentrations are independent of CB1Rs.",
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AU - Csölle, Cecília

AU - Sperlágh, B.

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N2 - Objective: Cannabinoids play an important role in the suppression of proinflammatory cytokine production in the periphery and brain. In this study, we explored whether endogenous activation of cannabinoid (CB) 1 receptors (CB1Rs) affects interleukin (IL)-1β levels in the mouse hippocampus under basal conditions and following stimulation with in vivo bacterial lipopolysaccharide (LPS, 250 μg/kg i.p.). Methods: IL-1β levels were determined in the hippocampi of wild-type (WT), CB1R-/- and P2X7 receptor (P2X7R)-/- mice using an ELISA kit. Results: Basal but not LPS-induced IL-1β levels were downregulated when CB1R function was abrogated by genetic deletion, suggesting that endocannabinoids contributed to basal IL-1β content in the mouse hippocampus. AM251 (3 mg/kg i.p.), an antagonist of CB1Rs, also inhibited basal IL-1β protein in WT but not in CB1R-/- mice. In the absence of P2X7R, LPS-induced IL-1β production was lower, while the inhibitory effect of CB1R antagonists on basal IL-1β was significantly attenuated. The LPS-induced elevation in IL-1β production was decreased in the presence of AM251 and AM281, with no significant difference between WT and P2X7R-/- mice. Conclusions: CB1Rs are responsible for the modulation of basal IL-1β levels in the hippocampus, while the effects of CB1 antagonists on systemic LPS-induced IL-1β concentrations are independent of CB1Rs.

AB - Objective: Cannabinoids play an important role in the suppression of proinflammatory cytokine production in the periphery and brain. In this study, we explored whether endogenous activation of cannabinoid (CB) 1 receptors (CB1Rs) affects interleukin (IL)-1β levels in the mouse hippocampus under basal conditions and following stimulation with in vivo bacterial lipopolysaccharide (LPS, 250 μg/kg i.p.). Methods: IL-1β levels were determined in the hippocampi of wild-type (WT), CB1R-/- and P2X7 receptor (P2X7R)-/- mice using an ELISA kit. Results: Basal but not LPS-induced IL-1β levels were downregulated when CB1R function was abrogated by genetic deletion, suggesting that endocannabinoids contributed to basal IL-1β content in the mouse hippocampus. AM251 (3 mg/kg i.p.), an antagonist of CB1Rs, also inhibited basal IL-1β protein in WT but not in CB1R-/- mice. In the absence of P2X7R, LPS-induced IL-1β production was lower, while the inhibitory effect of CB1R antagonists on basal IL-1β was significantly attenuated. The LPS-induced elevation in IL-1β production was decreased in the presence of AM251 and AM281, with no significant difference between WT and P2X7R-/- mice. Conclusions: CB1Rs are responsible for the modulation of basal IL-1β levels in the hippocampus, while the effects of CB1 antagonists on systemic LPS-induced IL-1β concentrations are independent of CB1Rs.

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