Cannabinoid receptors modulate LPS-induced increase of class-II transactivator expression levels in a microglial cell...

Microglial antigen generation (MAG) is an essential process in regulating disease states and homeostasis of the central nervous system. MAG is considered as responsible autoimmune mechanism in neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Neuroprotective and regulator effects of cannabinoid receptors on these disease states and modulation with pharmacological agents are urgent subjects in recent decades. Although different aspects of microglial immune response have been investigated, specific effects of these receptor subtypes in the MAG are still unclear. Therefore, in the current study, we have investigated the effects of CB₁ and CB₂ receptors on antigen generation by investigating MHC-II and its master regulator CIITA by specific cannabinoid agents (ACEA, AM-251, CP 55,940, and SR144528) in the LPS-induced BV-2 cells. Additionally, the effects of drug treatments on inflammatory status were measured by determining IL-1β, IL-6, and TNF-α levels. LPS-induced increase in MHC-II and CIITA expression was inhibited by specific CB₁ agonist, ACEA, and nonselective cannabinoid agonist CP 55,940. A combination with specific CB₁ antagonist AM-251 prevented these inhibitory effects of ACEA and CP 55,940 on both MHC-II and CIITA expression. Although specific CB₂ antagonist, SR144528, also prevented the inhibitory effect of CP 55,940 on MHC-II, it did not affect CIITA expression. LPS-induced IL-1β, IL-6, and TNF-α increase both attenuated with CP 55,940 and ACEA treatments. Although both selective cannabinoid antagonists inhibited this effect, preventive effects were more dominant on CB₁ receptors. Our results demonstrated that CB₁ receptors majorly mediates LPS-induced MHC-II and its regulator CIITA expression in microglial cells.