Table 1.

Effects of eCB modulation on microglial polarization in vitro.

Treatment	Cell culture	eCB activation method	M1/M2 phenotype	Other key findings/antagonist tests	References
LPS (1 μg/mL) 24 h	mouse primary MG	BCP (1 μM) 24 h prior to LPS	IL-1β/TNFα/PGE2/iNOS/NO/ROS ↓; IL-10/urea/Arg1/GSH ↑	cell proliferation up; AM630 (1 μM) but not GW9662 (1 μM) reversed	(80)
LPS (100 ng/mL) 8–24 h	BV2	PF3845 (10 μM), URB597 (10 μM) 30 min prior to LPS: FAAH siRNA	PF and URB: PGE2/COX-2/iNOS/IL-6/IL-1β/MCP-1 ↓; IL-10/IL-4/Arg1/Ym1 no change; siRNA: PGE2/COX-2/iNOS/IL-6/IL-1β/MCP-1 ↓; IL-10/IL-4 ↑; Arg1/Ym1 ↑ w/o LPS	SR1/SR2/GW6471/GW9662/O1918 no effect	(81)
LPS (10 ng/mL) + IFNγ (10 U/mL) 3 h	N9	AM1241(10 μM) co-incubated	TNFα/iNOS ↓; Arg1/BDNF ↑	mitochondria/mtDNA/ATP/complex1 &4/Nrf1/Tfam/COX IV/MMP ↑; PGC-1α knockdown reversed	(82)
IFNγ (100 U/mL) + WIN55,212-2 (1 μM) 25 h	BV2	SR1 (1 μM) 1 h post IFNγ/WIN	IL-10 ↓; NO release ↑; MCP-1/TNFα/IL-1β/IL-6/IL-17/IFNγ/CX3CL1 ↑	IL-4/IL-10 ↓ and IFNγ/IL-17 ↑ in CD4+ T cells cultured in BV2 conditioned medium with SR1	(83)
	BV2	VCE004.8 (1 μM) 24 h	Arg1/PPARγ ↑	SR2 no effect; GW9662 no effect	(84)
LPS (25 ng/mL) 24 h	BV2	EEQ-EA (5-10 μM) or EDP-EA (5–10 μM) 4 h prior to LPS	IL-6/nitrite/cytotoxicity ↓; IL-10 ↑	AM630 (1 μM) reversed; eCB metabolites by CYP450 detected in brain; antiangiogenic	(85)
thrombin (20 U/mL) 48 h	rat primary MG	JWH133 (4 μM) 24 h post thrombin	IFNγ/CD86/CD68/IL-1β/TNFα ↓; TGFβ/IL-4/IL-10/CD206/Ym1 ↑	AM630 (1 μM) reversed; PKA inhibitor reversed; cAMP/P-PKA/Epac1 ↑	(86)
LPS (100 ng/mL) 24 h	rat primary MG	AEA (1 μM) 15 min prior to LPS	IL-6/COX-2/iNOS/NO ↓; IL-1β/IL-18/TNFα no change; IL-10/NGF ↑	AM630 but not AM251/CID1602 reversed NO release; AM630 reversed IL-18/TNFα/COX-2	(87)
LPS (50 ng/mL), IL-4 (10 ng/mL) + IL-13 (10 ng/mL), or TGFβ (20 ng/mL) 6 or 24 h	rat, mouse, or human primary MG	2-AG (1 nM) or AEA (1 nM) 24 h	2-AG but not AEA ↑ in M2a (IL-4/IL-13); AEA but not 2-AG ↑ in M2c (TGFβ); Arg1/SOCS3/CB1 ↑ by 2-AG; Arg1/SOCS3/CB2 ↑ by AEA	AM251 (1 μM) and AM630 (1 μM) 0.5 h prior to IL-4/IL-13 reversed Arg1; CB2 KO ↓ Arg1/phagocytosis	(88)
LPS (1 μg/mL) 12 or 24 h	C8B4, human primary MG	SMM-189 1 h post LPS	CD16/32 ↓; CD206 ↑; rod-shape ↑; round/amoeboid shape ↓; eotaxin/IP10/MCP-1/ TARC/MIP-1β ↓	HU308/JWH133: CD16/32 and CD206 ↓; SR2: CD206 but not CD16/32 ↑	(89)
LPS (1 μg/mL) 24 h	BV2, mouse primary MG	JZL184 (1 μM) 1 h prior to LPS; MAGL overexpression	JZL: Fcγ-induced phagocytosis ↓; inflammatory cytokines/iNOS no change (primary MG); MAGL overexpression: Fcγ-induced phagocytosis ↑ (BV2)	phagocytosis Fcγ-mediated; MG132 reversed effects of MAGL; MAGL knockdown no effect	(90)
LPS (10 ng/mL) + IFNγ (10 U/mL) 24 h	N9 MG	AM1241 (5 μM) 1 h prior to LPS	Arg1/IL-10/BDNF/GDNF ↑; iNOS/IL-1β/IL-6/TNFα ↓	AM630 (10 μM) reversed; PKC inhibitor (10 μM) reversed	(91)
LPS (1 μg/mL or 0.1 μg/mL) 18 or 24 h	human primary or immortalized MG	SMM-189 (9.8 μM) 1 h post LPS or (13.4 μM) co-treated with LPS or IL-4	CD11b/CD45/CD80 ↓; IL-8/chemokines/IFNγ/IL-6/IL-12/IL-10 ↓; CD206 ↑ in IL-4 co-treated	LPS/IFNγ/IL-10/IL-4 ↑ CB2	(92)
LPS (50 ng/mL) + IFNγ (100 U/mL) 24 h	mouse primary MG and neuron mix	AEA (10 μM) co-treatment	IL-1β/IL-6 ↓; IL-10 ↑	ERK/JNK signal involved; CD200R ↑; neuron death ↓; CD200R KO and CD200 Ab reversed	(93)
TMEV infection at MOI (5 PFU/cell) 18 or 24 h	mouse primary MG	AEA (10 μM) co-treatment	IL-12/IL-23/IL-17A/NFκB ↓; IL-10 ↑	SR2 (1 μM) not SR1 (1 μM) reversed; Erk/Jnk inhibitor reversed; IL-10 Ab reversed IL-12/IL-23	(94)
LPS (50 ng/mL) + IFNγ (100 U/mL) 24 h	mouse primary MG	AEA (10 μM) co-treatment	NFκB/IL-12/IL-23/P-IκBα ↓; IL-10 ↑	ERK1/2/JNK/NFκB pathways involved; SR2 reversed; AEA treated conditioned medium down T-bet (Th1) but up GATA3 (Th2) in splenocyte	(95)

↓↑, increased or decreased by eCB treatment, respectively; Ab, antibody; h, hour; KO, knockout mouse; MG, microglia.