Cannabinoid receptor 1 promotes M1 polarization of macrophages through the Gαi/o/RhoA signaling pathway in mice with acute lung injury
10.3969/j.issn.1674-8115.2025.02.004
- VernacularTitle:大麻素受体1通过Gαi/o/RhoA信号通路促进急性肺损伤小鼠巨噬细胞M1极化
- Author:
Xiuzhen MA
1
;
Ni ZHOU
;
Siqi GUO
;
Yuanyuan WANG
;
Ping MAI
Author Information
1. 兰州大学第一临床医学院,兰州 730099;甘肃省人民医院消化内科,兰州 730030
- Publication Type:Journal Article
- Keywords:
acute lung injury(ALI);
cannabinoid receptor 1(CB1);
macrophage;
M1 type polarization;
Gαi/o/RhoA signaling pathway
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2025;45(2):161-168
- CountryChina
- Language:Chinese
-
Abstract:
Objective·To explore the effects and potential molecular mechanisms of blocking cannabinoid receptor 1(CB1)in acute lung injury(ALI)in mice.Methods·Forty mice were randomly divided into blank control group,AM281(CB1 antagonist)control group,lipopolysaccharide(LPS)group,and LPS+AM281 group,with ten mice in each group.ALI models were induced by LPS.The pathological manifestations of lung tissues were observed in each group of mice by hematoxylin and eosin(H-E)staining and the inflammation scores were calculated.The mRNA levels of M1 markers[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-12]and M2 markers[arginase(Arg),mannose receptor,C type 2(Mrc2),macrophage galactose-type lectin 1(Mgl1)]in lung macrophages were measured by reverse transcription and real-time fluorescence quantitative polymerase chain reaction(qPCR).Human myeloid leukemia monocytes THP-1 cells were cultured in vitro,and the expression of CB1 and CB2 in THP-1 cells was detected by immunofluorescence.After further blocking CB1 and inhibiting the Gαi/o/RhoA signaling pathway,the mRNA levels of M1 markers were assessed.Results·The LPS group showed significant lung tissue damage and a significant increase in inflammation scores in mice.After blocking CB1,compared with the LPS group,the LPS+AM281 group of mice showed improvements in lung injury,manifested as improved congestion of alveolar wall capillaries,reduced infiltration of inflammatory cells in the lung interstitium and alveolar cavity,and a decreased inflammation score(P=0.007).Compared with the control group,the levels of M1 marker in the lung tissue of the LPS group were upregulated,while the polarization of macrophages changed and the M1/M2 ratio was reversed after blocking CB1(all P<0.05).In vitro studies found that macrophages expressed CB1 and CB2.Activation of CB1 by arachidonyl-2-chloroethylamide(ACEA)upregulated the expression of M1 markers.Blocking CB1 and selectively inhibiting Gαi/o/RhoA signaling significantly downregulated M1 markers(all P<0.05).Conclusion·CB1 promotes the polarization of macrophage towards the M1 phenotype through the Gαi/o/RhoA signaling pathway in ALI,and blocking CB1 can improve lung injury.
