title: Morphine promotes apoptosis via TLR2, and this is negatively regulated by beta-arrestin 2.
abstract: We have previously reported that morphine induces apoptosis. However, the underlying molecular mechanisms remain to be elucidated. Toll-like receptor 2 (TLR2), a key immune receptor in the TLR family, modulates cell survival and cell death in various systems. Evidence indicates that beta-arrestin 2 acts as a negative regulator of innate immune activation by TLRs. Here, we investigated the roles of TLR2, the downstreaming mediator MyD88, and beta-arrestin 2 in morphine-induced apoptosis. We showed that overexpression of TLR2 in HEK293 cells caused a significant increase in apoptosis after morphine treatment. Inhibition of MyD88 by transfecting dominant negative MyD88 or overexpression of beta-arrestin 2 by transfecting beta-arrestin 2 full length plasmid in TLR2 overexpressing HEK293 cells attenuated morphine-induced apoptosis. Our study thus demonstrates that TLR2 signaling mediates the morphine-induced apoptosis, and beta-arrestin 2 is a negative regulator in morphine-induced, TLR2-mediated apoptosis.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Xiuli
authors.initials: X
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Huang
authors.forename: Gregory
authors.initials: G
authors.lastname: Hanley
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Ferslew
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Deling
authors.initials: D
authors.lastname: Yin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D019390:Arrestins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002460:Cell Line; D006801:Humans; D007113:Immunity, Innate; D009020:Morphine / Q000494:pharmacology*; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605254:ARRB2 protein, human; D019390:Arrestins; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D009020:Morphine