Toll-like receptor 2 is required for opioids-induced neuronal apoptosis

Yi Li, Hui Li, Yi Zhang, Xiuli Sun, Gregory A. Hanley, Gene LeSage, Ying Zhang, Shenggang Sun, Ying Peng, Deling Yin

Research output: Contribution to journalArticle

Abstract

Toll-like receptor 2 (TLR2), a key immune receptor in the TLR family, is widely expressed in various systems, including the immune and nervous systems and plays a critical role in controlling innate and adaptive immune responses. We previously reported that opioids inhibit cell growth and trigger apoptosis. However, the underlying mechanism by which TLR2 mediates apoptosis in response to opioids is not yet known. Here we show that chronic morphine treatment in primary neurons dramatically increased the expression of TLR2 at both the messenger RNA and protein levels. In addition, TLR2 deficiency significantly inhibited chronic morphine-induced apoptosis in primary neurons. Activation of caspase-3 after morphine treatment is impaired in TLR2 deficient primary neurons. Moreover, morphine treatment failed to induce an increased level of phosphorylated glycogen synthase kinase 3 beta (GSK3β) in TLR2 deficient primary neurons, suggesting an involvement of GSK3β in morphine-mediated TLR2 signaling. These results thus demonstrate that opioids prime neurons to undergo apoptosis by inducing TLR2 expression. Our data suggest that inhibition of TLR2 is capable of preventing opioids-induced damage to neurons.

Original languageEnglish (US)
Pages (from-to)426-430
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume391
Issue number1
DOIs
StatePublished - Jan 1 2010

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Toll-Like Receptor 2
Opioid Analgesics
Apoptosis
Neurons
Morphine
Glycogen Synthase Kinase 3
Immune system
Cell growth
Neurology
Adaptive Immunity
Innate Immunity
Caspase 3
Nervous System
Immune System
Chemical activation
Messenger RNA

Keywords

  • Apoptosis
  • Morphine
  • Neurons
  • TLR2

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Toll-like receptor 2 is required for opioids-induced neuronal apoptosis. / Li, Yi; Li, Hui; Zhang, Yi; Sun, Xiuli; Hanley, Gregory A.; LeSage, Gene; Zhang, Ying; Sun, Shenggang; Peng, Ying; Yin, Deling.

In: Biochemical and Biophysical Research Communications, Vol. 391, No. 1, 01.01.2010, p. 426-430.

Research output: Contribution to journalArticle

Li, Y, Li, H, Zhang, Y, Sun, X, Hanley, GA, LeSage, G, Zhang, Y, Sun, S, Peng, Y & Yin, D 2010, 'Toll-like receptor 2 is required for opioids-induced neuronal apoptosis', Biochemical and Biophysical Research Communications, vol. 391, no. 1, pp. 426-430. https://doi.org/10.1016/j.bbrc.2009.11.074
Li, Yi ; Li, Hui ; Zhang, Yi ; Sun, Xiuli ; Hanley, Gregory A. ; LeSage, Gene ; Zhang, Ying ; Sun, Shenggang ; Peng, Ying ; Yin, Deling. / Toll-like receptor 2 is required for opioids-induced neuronal apoptosis. In: Biochemical and Biophysical Research Communications. 2010 ; Vol. 391, No. 1. pp. 426-430.
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