Endocannabinoid 2-arachidonoylglycerol protects inflammatory insults from sulfur dioxide inhalation via cannabinoid receptors in the brain

J Environ Sci (China). 2017 Jan:51:265-274. doi: 10.1016/j.jes.2016.05.031. Epub 2016 Jul 19.


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 SO2 inhalation 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 SO2 inhalation 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 SO2 inhalation.

Keywords: 2-Arachidonoylglycerol; Cannabinoid receptors; Microvasculature dysfunction; Neuroinflammation; Sulfur dioxide.

MeSH terms

  • Air Pollutants / toxicity*
  • Anti-Inflammatory Agents
  • Arachidonic Acids / pharmacology*
  • Brain / metabolism*
  • Endocannabinoids / pharmacology*
  • Glycerides / pharmacology*
  • Inhalation Exposure / adverse effects
  • Nitric Oxide Synthase Type II / metabolism
  • Receptors, Cannabinoid / metabolism*
  • Sulfur Dioxide / toxicity*


  • Air Pollutants
  • Anti-Inflammatory Agents
  • Arachidonic Acids
  • Endocannabinoids
  • Glycerides
  • Receptors, Cannabinoid
  • Sulfur Dioxide
  • glyceryl 2-arachidonate
  • Nitric Oxide Synthase Type II