Surveys suggest that Cannabis provides benefit for people with inflammatory bowel disease. However, mechanisms underlying beneficial effects are not clear. We performed in situ hybridization RNAscope® combined with immunohistochemistry to show cell-specific distribution and regulation of cannabinoid receptor 1 and 2 (CB1, CB2), G protein-coupled receptor 55 (GPR55), and monoacylglycerol lipase (MGL) mRNA in immune cells using murine models of intestinal and systemic inflammation. In healthy animals, the presence in enteric ganglia is high for CB1 mRNA, but low for CB2 and GPR55 mRNAs. MGL mRNA is predominant throughout the intestinal wall including myenteric neurons, epithelium, circular and longitudinal muscular layers, and the lamina propria. Within the immune system, B220+ cells exhibit high gene expression for CB2 while the expression of CB2 in F4/80+ and CD3+ cells is less prominent. In contrast, GPR55 mRNA is highly present in F4/80+ and CD3+ cells. qRT-PCR of total colonic segments shows that the expression of GPR55 and MGL genes drops during intestinal inflammation. Also at cellular levels, GPR55 and MGL gene expression is reduced in F4/80+, but not CD3+ cells. As to systemic inflammation, reduced gene expression of MGL is observed in ileum by qRT-PCR, while at cellular levels, altered gene expression is also seen for CB1 and GPR55 in CD3+ but not F4/80+ cells. In summary, our study reveals changes in gene expression of members of the endocannabinoid system in situ attesting particularly GPR55 and MGL a distinct cellular role in the regulation of the immune response to intestinal and systemic inflammation.

中文翻译：

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肠道和全身炎症中内源性大麻素系统的受体和酶的细胞定位和调节。

调查表明，大麻为患有炎症性肠病的人带来好处。但是，尚不清楚潜在的有益机制。我们进行了原位杂交RNAscope®与免疫组织化学的结合，以显示免疫细胞中大麻素受体1和2（CB1，CB2），G蛋白偶联受体55（GPR55）和单酰基甘油脂酶（MGL）mRNA的细胞特异性分布和调控使用肠道和全身炎症的鼠模型。在健康动物中，肠神经节中CB1 mRNA的表达较高，而CB2和GPR55 mRNA的表达较低。MGL mRNA在整个肠壁中占主导地位，包括肌层神经元，上皮，圆形和纵向肌肉层以及固有层。在免疫系统中 B220 +细胞对CB2的基因表达较高，而CB2在F4 / 80 +和CD3 +细胞中的表达较少。相反，GPR55 mRNA在F4 / 80 +和CD3 +细胞中高度存在。总结肠节段的qRT-PCR显示，肠道炎症期间GPR55和MGL基因的表达下降。同样在细胞水平上，GPR55和MGL基因表达在F4 / 80 +细胞中降低，但在CD3 +细胞中不降低。对于全身性炎症，通过qRT-PCR在回肠中观察到MGL基因表达降低，而在细胞水平上，CD3 +中的CB1和GPR55基因表达也发生了改变，而F4 / 80 +细胞中没有。综上所述，