Pulmonary Disfunction after Polysubstance Exposure: Mechanistic Identification of Inflammatory Mediators

摘要 酒精和大麻（大麻素）是世界范围内普遍滥用的药物，青少年 这两种药物的共同接触/共同滥用的特点是共同发病率高。两者都是慢性的 酒精和大麻素的过度消耗增加了急性肺损伤（ALI）的风险， 社区和卫生保健相关肺炎（分别为CAP和HAP），导致增加 发病率和死亡率。我们最近利用小鼠模型为青少年间歇乙醇 (AIE)和大麻素（AIC）暴露，以检查成人肺 炎症，我们的数据表明，先前的多物质暴露导致增加 HMGB 1表达与微生物诱导的肺部炎症有趣的是，我们的体外研究 表明酒精和大麻素都能激活巨噬细胞HMGB-1表达， 抑制细胞上的大麻素受体CB 1 R和CB 2 R抑制HMGB-1表达， 使用CB 1 R的拮抗剂在体内重现。我们的目标是研究CBR信号作为一种潜在的 酒精和大麻素依赖性肺部炎症的治疗方向。

Abstract Alcohol and marijuana (cannabinoids) are commonly abused drugs worldwide, and adolescent co-exposure/co-abuse of these two drugs is hallmarked by high levels of co-morbidity. Both chronic binge ethanol and cannabinoid consumption enhances the risk of acute lung injury (ALI) and both community and health care associated pneumonia (CAP and HAP, respectively), leading to increased morbidity and mortality. We have recently utilized a mouse model for adolescent intermittent ethanol (AIE) and cannabinoid (AIC) exposure to examine roles of binge exposure to adult-pulmonary inflammation, and our data suggests that that the prior polysubstance exposure leads to increased HMGB1 expression and microbial-induced pulmonary inflammation. Interestingly, our in vitro studies indicate that both alcohol and cannabinoids activate HMGB-1 expression from macrophage cells, and inhibiting cannabinoid receptors CB1R and CB2R on cells inhibits HMGB-1 expression, and is recapitulated in vivo using antagonists for CB1R. We aim to investigate CBR signaling as a potential therapeutic direction in response to alcohol and cannabinoid-dependent pulmonary inflammation.