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Δ(9)-THC and N-arachidonoyl glycine regulate BV-2 microglial morphology and cytokine release plasticity: implications for signaling at GPR18.
Front Pharmacol. 2014; 4:162.FP

Abstract

Microglial cells are extremely plastic and undergo a variety of CNS-prompted shape changes relative to their location and current role. Signaling molecules from neurons also regulate microglial cytokine production. Neurons are known to employ the endogenous cannabinoid system to communicate with other cells of the CNS. N-arachidonoyl glycine (NAGly) and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) signaling via GPR18 has been introduced as an important new target in microglial-neuronal communication. Our hypothesis is that endogenous NAGly-GPR18 signaling regulates phenotypic shape and cytokine production in microglia, and is mimicked by Δ(9)-THC in the BV-2 microglia model system. BV-2 microglia were exposed to NAGly and Δ(9)-THC or Vh for 12 h, which resulted in significant differences in the cell morphologies expressed. Cannabidiol (CBD) was effective at antagonizing the effects of both NAGly and Δ(9)-THC. Using ELISA-based microarrays, BV-2 microglia were exposed to NAGly and Δ(9)-THC or Vh for 3 h and the presence of 40 cytokines in the culture media quantified. Production of Axl, CD40, IGF-I, OPN, and Pro-MMP-9 were significantly altered by NAGly and Δ(9)-THC, and antagonized by CBD. These data add to an emerging profile that emphasizes NAGly as a component of an endogenous system present in the CNS that tightly integrates microglial proliferation, recruitment, and adhesion with neuron-glia interactivity and tissue remodeling.

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Authors+Show Affiliations

McHugh D
Department of Psychological and Brain Sciences, Indiana University Bloomington, IN, USA ; Frank H. Netter MD School of Medicine, Quinnipiac University North Haven, CT, USA.
Roskowski D
Department of Psychological and Brain Sciences, Indiana University Bloomington, IN, USA.
Xie S
Department of Psychological and Brain Sciences, Indiana University Bloomington, IN, USA.
Bradshaw HB
Department of Psychological and Brain Sciences, Indiana University Bloomington, IN, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24427137

Citation

McHugh, Douglas, et al. "Δ(9)-THC and N-arachidonoyl Glycine Regulate BV-2 Microglial Morphology and Cytokine Release Plasticity: Implications for Signaling at GPR18." Frontiers in Pharmacology, vol. 4, 2014, p. 162.
McHugh D, Roskowski D, Xie S, et al. Δ(9)-THC and N-arachidonoyl glycine regulate BV-2 microglial morphology and cytokine release plasticity: implications for signaling at GPR18. Front Pharmacol. 2014;4:162.
McHugh, D., Roskowski, D., Xie, S., & Bradshaw, H. B. (2014). Δ(9)-THC and N-arachidonoyl glycine regulate BV-2 microglial morphology and cytokine release plasticity: implications for signaling at GPR18. Frontiers in Pharmacology, 4, 162. https://doi.org/10.3389/fphar.2013.00162
McHugh D, et al. Δ(9)-THC and N-arachidonoyl Glycine Regulate BV-2 Microglial Morphology and Cytokine Release Plasticity: Implications for Signaling at GPR18. Front Pharmacol. 2014;4:162. PubMed PMID: 24427137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Δ(9)-THC and N-arachidonoyl glycine regulate BV-2 microglial morphology and cytokine release plasticity: implications for signaling at GPR18. AU - McHugh,Douglas, AU - Roskowski,Daniel, AU - Xie,Sisi, AU - Bradshaw,Heather B, Y1 - 2014/01/02/ PY - 2013/08/31/received PY - 2013/12/09/accepted PY - 2014/1/16/entrez PY - 2014/1/16/pubmed PY - 2014/1/16/medline KW - BV-2 KW - GPR18 KW - NAGly KW - cytokine KW - microglia KW - morphology KW - phenotype KW - Δ9-THC SP - 162 EP - 162 JF - Frontiers in pharmacology JO - Front Pharmacol VL - 4 N2 - Microglial cells are extremely plastic and undergo a variety of CNS-prompted shape changes relative to their location and current role. Signaling molecules from neurons also regulate microglial cytokine production. Neurons are known to employ the endogenous cannabinoid system to communicate with other cells of the CNS. N-arachidonoyl glycine (NAGly) and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) signaling via GPR18 has been introduced as an important new target in microglial-neuronal communication. Our hypothesis is that endogenous NAGly-GPR18 signaling regulates phenotypic shape and cytokine production in microglia, and is mimicked by Δ(9)-THC in the BV-2 microglia model system. BV-2 microglia were exposed to NAGly and Δ(9)-THC or Vh for 12 h, which resulted in significant differences in the cell morphologies expressed. Cannabidiol (CBD) was effective at antagonizing the effects of both NAGly and Δ(9)-THC. Using ELISA-based microarrays, BV-2 microglia were exposed to NAGly and Δ(9)-THC or Vh for 3 h and the presence of 40 cytokines in the culture media quantified. Production of Axl, CD40, IGF-I, OPN, and Pro-MMP-9 were significantly altered by NAGly and Δ(9)-THC, and antagonized by CBD. These data add to an emerging profile that emphasizes NAGly as a component of an endogenous system present in the CNS that tightly integrates microglial proliferation, recruitment, and adhesion with neuron-glia interactivity and tissue remodeling. SN - 1663-9812 UR - https://www.unboundmedicine.com/medline/citation/24427137/Δ_9__THC_and_N_arachidonoyl_glycine_regulate_BV_2_microglial_morphology_and_cytokine_release_plasticity:_implications_for_signaling_at_GPR18_ DB - PRIME DP - Unbound Medicine ER -