Title
Morphine Promotes Apoptosis via TLR2, and This Is Negatively Regulated by β-Arrestin 2
Document Type
Article
Publication Date
1-23-2009
Description
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 β-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 β-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 β-arrestin 2 by transfecting β-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 β-arrestin 2 is a negative regulator in morphine-induced, TLR2-mediated apoptosis.
Citation Information
Li, Yi; Sun, Xiu L.; Zhang, Yi; Huang, Jing J.; Hanley, Gregory; Ferslew, Kenneth E.; Peng, Ying; and Yin, De Ling. 2009. Morphine Promotes Apoptosis via TLR2, and This Is Negatively Regulated by β-Arrestin 2. Biochemical and Biophysical Research Communications. Vol.378(4). 857-861. https://doi.org/10.1016/j.bbrc.2008.12.001 PMID: 19071087 ISSN: 0006-291X