L-type calcium channels and μ-opioid receptors are involved in mediating the anti-inflammatory effects of naloxone

Woan Ching Jan, Cay Huyen Chen, Kuei Hsu, Pei Shan Tsai, Chun Jen Huang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: We sought to elucidate the effects of naloxone on regulating the up-regulation of inflammatory molecules and activation of the transcription factor nuclear factor-kappaB (NF-κB) induced by endotoxin. Possible roles of the μ-opioid receptors and L-type calcium channels in mediating the effects of naloxone in this regard were also investigated. Materials and Methods: RAW264.7 cells were treated with phosphate buffered saline, naloxone, lipopolysaccharide (LPS), LPS plus naloxone, LPS plus naloxone plus morphine (i.e., the nonselective opioid receptors agonist), LPS plus naloxone plus fentanyl (i.e., the μ-opioid receptors agonist), or LPS plus naloxone plus BAY-K8644 (i.e., the L-type calcium channel activator). After harvesting, production of inflammatory molecules and expression NF-κB were evaluated. Results: The effects of LPS on inducing the up-regulation of macrophage inflammatory protein-2, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide/inducible nitric oxide synthase, and prostaglandin E 2/cyclooxygenase 2 were inhibited by naloxone. Naloxone also inhibited the effects of LPS on inducing NF-κB activation, including inhibitor-κB (I-κB) degradation, NF-κB nuclear translocation, and NF-κB-DNA binding. The effects of naloxone on inhibiting IL-1β up-regulation and NF-κB activation were enhanced by morphine. In contrast, the effects of naloxone on inhibiting IL-1β up-regulation and I-κB degradation were counteracted by fentanyl. Moreover, except for TNF-α, the effects of naloxone on inhibiting inflammatory molecules up-regulation and NF-κB activation were significantly counteracted by BAY-K8644. Conclusions: Naloxone significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-κB activation. The mechanisms may involve antagonizing the L-type calcium channels and, to a lesser extent, the μ-opioid receptors.

Original languageEnglish
JournalJournal of Surgical Research
Volume167
Issue number2
DOIs
Publication statusPublished - May 15 2011

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L-Type Calcium Channels
Opioid Receptors
Naloxone
Anti-Inflammatory Agents
Lipopolysaccharides
Up-Regulation
Interleukin-1
Fentanyl
Endotoxins
Morphine
Tumor Necrosis Factor-alpha
Calcium Channel Agonists
Chemokine CXCL2
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Prostaglandins E
Interleukin-6
Nitric Oxide

Keywords

  • chemokine
  • cytokine
  • endotoxin
  • macrophages
  • NF-κB

ASJC Scopus subject areas

  • Surgery

Cite this

L-type calcium channels and μ-opioid receptors are involved in mediating the anti-inflammatory effects of naloxone. / Jan, Woan Ching; Chen, Cay Huyen; Hsu, Kuei; Tsai, Pei Shan; Huang, Chun Jen.

In: Journal of Surgical Research, Vol. 167, No. 2, 15.05.2011.

Research output: Contribution to journalArticle

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abstract = "Background: We sought to elucidate the effects of naloxone on regulating the up-regulation of inflammatory molecules and activation of the transcription factor nuclear factor-kappaB (NF-κB) induced by endotoxin. Possible roles of the μ-opioid receptors and L-type calcium channels in mediating the effects of naloxone in this regard were also investigated. Materials and Methods: RAW264.7 cells were treated with phosphate buffered saline, naloxone, lipopolysaccharide (LPS), LPS plus naloxone, LPS plus naloxone plus morphine (i.e., the nonselective opioid receptors agonist), LPS plus naloxone plus fentanyl (i.e., the μ-opioid receptors agonist), or LPS plus naloxone plus BAY-K8644 (i.e., the L-type calcium channel activator). After harvesting, production of inflammatory molecules and expression NF-κB were evaluated. Results: The effects of LPS on inducing the up-regulation of macrophage inflammatory protein-2, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide/inducible nitric oxide synthase, and prostaglandin E 2/cyclooxygenase 2 were inhibited by naloxone. Naloxone also inhibited the effects of LPS on inducing NF-κB activation, including inhibitor-κB (I-κB) degradation, NF-κB nuclear translocation, and NF-κB-DNA binding. The effects of naloxone on inhibiting IL-1β up-regulation and NF-κB activation were enhanced by morphine. In contrast, the effects of naloxone on inhibiting IL-1β up-regulation and I-κB degradation were counteracted by fentanyl. Moreover, except for TNF-α, the effects of naloxone on inhibiting inflammatory molecules up-regulation and NF-κB activation were significantly counteracted by BAY-K8644. Conclusions: Naloxone significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-κB activation. The mechanisms may involve antagonizing the L-type calcium channels and, to a lesser extent, the μ-opioid receptors.",
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T1 - L-type calcium channels and μ-opioid receptors are involved in mediating the anti-inflammatory effects of naloxone

AU - Jan, Woan Ching

AU - Chen, Cay Huyen

AU - Hsu, Kuei

AU - Tsai, Pei Shan

AU - Huang, Chun Jen

PY - 2011/5/15

Y1 - 2011/5/15

N2 - Background: We sought to elucidate the effects of naloxone on regulating the up-regulation of inflammatory molecules and activation of the transcription factor nuclear factor-kappaB (NF-κB) induced by endotoxin. Possible roles of the μ-opioid receptors and L-type calcium channels in mediating the effects of naloxone in this regard were also investigated. Materials and Methods: RAW264.7 cells were treated with phosphate buffered saline, naloxone, lipopolysaccharide (LPS), LPS plus naloxone, LPS plus naloxone plus morphine (i.e., the nonselective opioid receptors agonist), LPS plus naloxone plus fentanyl (i.e., the μ-opioid receptors agonist), or LPS plus naloxone plus BAY-K8644 (i.e., the L-type calcium channel activator). After harvesting, production of inflammatory molecules and expression NF-κB were evaluated. Results: The effects of LPS on inducing the up-regulation of macrophage inflammatory protein-2, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide/inducible nitric oxide synthase, and prostaglandin E 2/cyclooxygenase 2 were inhibited by naloxone. Naloxone also inhibited the effects of LPS on inducing NF-κB activation, including inhibitor-κB (I-κB) degradation, NF-κB nuclear translocation, and NF-κB-DNA binding. The effects of naloxone on inhibiting IL-1β up-regulation and NF-κB activation were enhanced by morphine. In contrast, the effects of naloxone on inhibiting IL-1β up-regulation and I-κB degradation were counteracted by fentanyl. Moreover, except for TNF-α, the effects of naloxone on inhibiting inflammatory molecules up-regulation and NF-κB activation were significantly counteracted by BAY-K8644. Conclusions: Naloxone significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-κB activation. The mechanisms may involve antagonizing the L-type calcium channels and, to a lesser extent, the μ-opioid receptors.

AB - Background: We sought to elucidate the effects of naloxone on regulating the up-regulation of inflammatory molecules and activation of the transcription factor nuclear factor-kappaB (NF-κB) induced by endotoxin. Possible roles of the μ-opioid receptors and L-type calcium channels in mediating the effects of naloxone in this regard were also investigated. Materials and Methods: RAW264.7 cells were treated with phosphate buffered saline, naloxone, lipopolysaccharide (LPS), LPS plus naloxone, LPS plus naloxone plus morphine (i.e., the nonselective opioid receptors agonist), LPS plus naloxone plus fentanyl (i.e., the μ-opioid receptors agonist), or LPS plus naloxone plus BAY-K8644 (i.e., the L-type calcium channel activator). After harvesting, production of inflammatory molecules and expression NF-κB were evaluated. Results: The effects of LPS on inducing the up-regulation of macrophage inflammatory protein-2, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, nitric oxide/inducible nitric oxide synthase, and prostaglandin E 2/cyclooxygenase 2 were inhibited by naloxone. Naloxone also inhibited the effects of LPS on inducing NF-κB activation, including inhibitor-κB (I-κB) degradation, NF-κB nuclear translocation, and NF-κB-DNA binding. The effects of naloxone on inhibiting IL-1β up-regulation and NF-κB activation were enhanced by morphine. In contrast, the effects of naloxone on inhibiting IL-1β up-regulation and I-κB degradation were counteracted by fentanyl. Moreover, except for TNF-α, the effects of naloxone on inhibiting inflammatory molecules up-regulation and NF-κB activation were significantly counteracted by BAY-K8644. Conclusions: Naloxone significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-κB activation. The mechanisms may involve antagonizing the L-type calcium channels and, to a lesser extent, the μ-opioid receptors.

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