| First Author | Olabiyi BF | Year | 2023 |
| Journal | Sci Rep | Volume | 13 |
| Issue | 1 | Pages | 11105 |
| PubMed ID | 37429837 | Mgi Jnum | J:337907 |
| Mgi Id | MGI:7508718 | Doi | 10.1038/s41598-023-37702-z |
| Citation | Olabiyi BF, et al. (2023) Pharmacological blockade of cannabinoid receptor 2 signaling does not affect LPS/IFN-gamma-induced microglial activation. Sci Rep 13(1):11105 |
| abstractText | Cannabinoid receptor 2 (CB2) signaling modulates microglial responses to inflammatory stimuli. Our previous studies demonstrated that genetic deletion of CB2 inhibits microglial activation during inflammatory stimulation of toll-like receptors (TLRs) or in neurodegenerative conditions. However, we cannot exclude developmental effects of the constitutive CB2 knockout (CB2(-/-)), which could mediate compensatory outcomes in CB2(-/-) mice. In the present study, we therefore tested whether acute pharmacological inhibition of CB2 receptor has a similar effect on microglial activation as in CB2(-/-) in response to inflammatory stimulation. Our findings suggest that the CB2-specific antagonist SR144528 has little or no effect on LPS/IFN-gamma-induced activation in primary microglia or organotypic hippocampal slice cultures at nanomolar concentrations. We show that SR144528 did not alter LPS/IFN-gamma-mediated microglial cytokine secretion, Iba1 and CD68 staining intensity or morphology at 1 and 10 nM. Although SR144528 suppressed LPS/IFN-gamma-induced microglial activation at 1 microM, this anti-inflammatory effect was not dependent on CB2 receptors and exceeded the Ki on CB2 receptors by more than a thousand-fold. Thus, SR144528 does not mimic the anti-inflammatory effects observed in the CB2(-/-) microglia after LPS/IFN-gamma stimulation. Therefore, we propose that the deletion of CB2 probably triggered an adaptive mechanism, making microglia less responsive to inflammatory stimulation. |
