Trans-caryophyllene suppresses hypoxia-induced neuroinflammatory responses by inhibiting NF-κB activation in microglia.
Microglia cells have been reported to mediate hypoxia-induced inflammation through the production of proinflammatory cytokines, including interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6. Given the fact that the activation of the type 2 cannabinoid receptor (CB2R) provides antioxidative and anti-inflammatory results, it is suspected that its selective agonist, trans-caryophyllene (TC), may have protective effects against hypoxia-induced neuroinflammatory responses. In this study, TC was found to significantly inhibit hypoxia-induced cytotoxicity as well as the release of proinflammatory cytokines, including IL-1β, TNF-α, and IL-6, through activation of BV2 microglia following hypoxic exposure (1 % O2, 24 h). Furthermore, TC significantly inhibited hypoxia-induced generation of reactive oxygen species (ROS) in mitochondria as well as the activation of nuclear factor kappa B (NF-κB) in microglia. Importantly, TC's effects on inhibiting the activation of NF-κB and the secretion of inflammatory cytokines can be abolished by muting the CB2R using small RNA interference. These observations indicate that TC suppresses the hypoxia-induced neuroinflammatory response through inhibition of NF-κB activation in microglia. Therefore, TC may be beneficial in preventing hypoxia-induced neuroinflammation.
Department of Neurology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Kexin
K
Guo
Xiaojie
X
Mou
Jinsha
J
Huang
Nian
N
Xiong
Hongge
H
Li
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015687:Cell Hypoxia; D002460:Cell Line; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D000081223:Polycyclic Sesquiterpenes; D017382:Reactive Oxygen Species / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D000081223:Polycyclic Sesquiterpenes; D017382:Reactive Oxygen Species; D043885:Receptor, Cannabinoid, CB2; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C024714:caryophyllene