title: Endocannabinoid 2-arachidonoylglycerol protects inflammatory insults from sulfur dioxide inhalation via cannabinoid receptors in the brain.
abstract: Sulfur dioxide (SO2) pollution in the atmospheric environment causes brain inflammatory insult and inflammatory-related microvasculature dysfunction. However, there are currently no effective medications targeting the harmful outcomes from chemical inhalation. Endocannabinoids (eCBs) are involved in neuronal protection against inflammation-induced neuronal injury. The 2-arachidonoylglycerol (2-AG), the most abundant eCBs and a full agonist for cannabinoid receptors (CB1 and CB2), is also capable of suppressing proinflammatory stimuli and improving microvasculature dysfunction. Here, we indicated that endogenous 2-AG protected against neuroinflammation in response to SO2inhalation by inhibiting the activation of microglia and astrocytes and attenuating the overexpression of inflammatory cytokines, including tumor necrosis factor alpha (TNF-a), interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS). In addition, endogenous 2-AG prevented cerebral vasculature dysfunction following SO2inhalation by inhibiting endothelin 1 (ET-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression, elevating endothelial nitric oxide synthase (eNOS) level, and restoring the imbalance between thromboxane A2 (TXA2) and prostaglandin I2 (PGI2). In addition, the action of endogenous 2-AG on the suppression of inflammatory insult and inflammatory-related microvasculature dysfunction appeared to be mainly mediated by CB1 and CB2 receptors. Our results provided a mechanistic basis for the development of new therapeutic approaches for protecting brain injuries from SO2inhalation.
authors.affiliation: College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Li
authors.affiliation: College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Chen
authors.affiliation: College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yun
authors.affiliation: College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China.
authors.forename: Guangke
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China. Electronic address: sangnan@sxu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Sang
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D063388:Endocannabinoids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D019570:Inhalation Exposure / Q000009:adverse effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D013458:Sulfur Dioxide / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D043882:Receptors, Cannabinoid; D013458:Sulfur Dioxide; C094503:glyceryl 2-arachidonate; D052247:Nitric Oxide Synthase Type II
keywords: 2-Arachidonoylglycerol; Cannabinoid receptors; Microvasculature dysfunction; Neuroinflammation; Sulfur dioxide