J Clin Invest. 2018 Aug 31;128(9):3750-3751. doi: 10.1172/JCI122885. Epub 2018 Aug 13.
Under normal conditions, there is a paucity of neutrophils within the intestinal mucosa; however, these innate immune cells rapidly infiltrate the mucosa in response to infection and are critical for pathogen control. Unfortunately, these cells can cause extensive damage to the intestine if the initial inflammatory influx is not resolved. Factors that promote resolution of inflammation are of great interest, as they have therapeutic potential for limiting uncontrolled inflammatory damage. In this issue of the JCI, Szabady et al. demonstrate that the multidrug resistance transporter P-glycoprotein (P-gp) secretes endocannabinoids into the intestinal lumen that counteract the proinflammatory actions of the eicosanoid hepoxilin A3, which is secreted into the lumen by the efflux pump MRP2 and serves as a potent neutrophil chemoattractant. Moreover, the antiinflammatory actions of P-gp-secreted endocannabinoids were mediated by peripheral cannabinoid receptor CB2 on neutrophils. Together, the results of this study identify an important mechanism by which endogenous endocannabinoids facilitate the resolution of inflammation; this mechanism has potential to be therapeutically exploited.
在正常情况下，肠道黏膜中中性粒细胞的数量很少；然而，这些先天免疫细胞会迅速浸润黏膜，以响应感染，对于病原体的控制至关重要。不幸的是，如果最初的炎症涌入得不到解决，这些细胞会对肠道造成广泛的损伤。促进炎症消退的因素是非常令人感兴趣的，因为它们具有治疗潜力，可以限制不受控制的炎症损伤。在本期 JCI 中，Szabady 等人表明，多药耐药转运蛋白 P-糖蛋白（P-gp）将内源性大麻素分泌到肠道腔中，抵消了由外排泵 MRP2 分泌到肠道腔中的二十烷类物质 hepoxilin A3 的促炎作用，后者是一种有效的中性粒细胞趋化因子。此外，P-gp 分泌的内源性大麻素对中性粒细胞外周大麻素受体 CB2 的抗炎作用具有介导作用。总之，这项研究的结果确定了内源性大麻素促进炎症消退的重要机制；该机制具有治疗潜力。
