Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official VSports app下载. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. V体育官网.

. 2014 Jan 2:4:162.
doi: 10.3389/fphar.2013.00162. eCollection 2014.

Δ(9)-THC and N-arachidonoyl glycine regulate BV-2 microglial morphology and cytokine release plasticity: implications for signaling at GPR18

Douglas McHugh  1 , Daniel Roskowski  2 , Sisi Xie  2 , Heather B Bradshaw  2
Affiliations

Δ(9)-THC and N-arachidonoyl glycine regulate BV-2 microglial morphology and cytokine release plasticity: implications for signaling at GPR18

"V体育官网" Douglas McHugh et al. Front Pharmacol. .

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 VSports手机版. 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. .

Keywords: BV-2; GPR18; NAGly; cytokine; microglia; morphology; phenotype; Δ9-THC. V体育安卓版.

PubMed Disclaimer

VSports注册入口 - Figures

FIGURE 1
FIGURE 1
Examples of the six different BV-2 morphological shapes observed and categorized.
FIGURE 2
FIGURE 2
Amoeboid versus branched phenotypes. Vehicle (0.1% DMS0), 10 nM PMA, 10 nM NAGly, 100 nM CBD, 10 nM NAGly + 100 nM CBD, 10 nM Δ9-THC, 10 nM Δ9-THC + 100 nM CBD. n = 5–15. *p < 0.05, **p < 0.01 (One-way ANOVA).
FIGURE 3
FIGURE 3
Levels of cytokine production after 3 h treatment in BV-2 microglia. (A) Axl, (B) IGF-1, (C) CD40, (D) OPN, (E) Pro-MMP-9. NAGly (10 nM and 100 nM) and Δ9-THC (10 nM and 100 nM). n = 4–5. *p < 0.05, **p < 0.01, ***p < 0.001 (One-way ANOVA).
FIGURE 4
FIGURE 4
Levels of cytokine production after 3 h treatment co-incubation with CBD in BV-2 microglia. (A) Axl, (B) IGF-1, (C) CD40, (D) OPN, (E) Pro-MMP-9. Cytokine production by BV-2 microglia in response to NAGly (10 nM) and Δ9-THC (100 nM) ± CBD (100 nM) n = 4–5. **p < 0.01, ***p < 0.001 (One-way ANOVA).
See this image and copyright information in PMC

References

    1. Begg M., Pacher P., Bátkai S., Osei-Hyiaman D., Offertáler L., Mo F. M., et al. (2005). Evidence for novel cannabinoid receptors. Pharmacol. Ther. 106133–14510.1016/j.pharmthera.2004.11.005 - DOI - PubMed
    1. Blasi E., Barluzzi R., Bocchini V., Mazzolla R., Bistoni F. (1990). Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus. J. Neuroimmunol. 27 229–23710.1016/0165-5728(90)90073-V - DOI - PubMed
    1. Block M. L., Zecca L., Hong J.-S. (2007). Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8 57–6910.1038/nrn2038 - DOI - PubMed
    1. Bradshaw H., Rimmerman N., Hu S., Benton V., Stuart J., Masuda K., et al. (2009). The endocannabinoid anandamide is a precursor for the signaling lipid N-arachidonoyl glycine by two distinct pathways. BMC Biochem. 10:14. 10.1186/1471-2091-10-14 - DOI - PMC - PubMed
    1. Cao L., Plamer C. D., Malon J. T, De Leo J. A. (2009). Critical role of microglial CD40 in the maintenance of mechanical hypersensitivity in a murine model of neuropathic pain. Eur. J. Immunol. 39 3562–356910.1002/eji.200939657 - DOI - PMC - PubMed