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MiR-582-5p/miR-590-5p targeted CREB1/CREB5-NF-κB signaling and caused opioid-induced immunosuppression in human

X Long1, Y Li1, S Qiu1

  • 1Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Translational Psychiatry
|March 16, 2016
PubMed

Insights

Opioid abuse weakens the immune system by reducing specific microRNAs (miRNAs). These miRNAs, miR-582-5p and miR-590-5p, normally regulate immune responses via the CREB1/CREB5-NF-κB pathway.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • Chronic opioid abuse is linked to increased susceptibility to infections.
  • The molecular mechanisms of opioid-induced immunosuppression remain poorly understood.
  • MicroRNAs (miRNAs) are critical regulators of biological processes, including immune function.

Purpose of the Study:

  • To investigate the role of miRNA dysregulation in opioid-induced immunosuppression.
  • To identify specific miRNAs and their molecular targets involved in this process.
  • To elucidate the signaling pathway affected by opioid exposure in monocytes.

Main Methods:

  • miRNA microarray analysis and quantitative PCR on blood samples from heroin abusers.
  • In vitro studies using primary human monocytes.
  • Dual-luciferase assay and Western blot to identify direct miRNA targets.
  • Functional studies involving knockdown of target genes.

Main Results:

  • Heroin and morphine significantly decreased the expression of miR-582-5p and miR-590-5p in monocytes.
  • CREB1 and CREB5 were identified as direct targets of miR-582-5p and miR-590-5p, respectively.
  • Knockdown of CREB1/CREB5 led to increased tumor necrosis factor alpha (TNF-α) and enhanced NF-κB signaling.

Conclusions:

  • miR-582-5p and miR-590-5p are crucial in opioid-induced immunosuppression in monocytes.
  • These miRNAs regulate immune responses by targeting the CREB1/CREB5-NF-κB signaling pathway.
  • Understanding this pathway offers potential targets for therapeutic interventions in opioid-abusing individuals.

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