title: MiR-582-5p/miR-590-5p targeted CREB1/CREB5-NF-κB signaling and caused opioid-induced immunosuppression in human monocytes.
abstract: Chronic opioid abusers are more susceptible to bacterial and viral infections, but the molecular mechanism underlying opioid-induced immunosuppression is unknown. MicroRNAs (miRNAs) are emerging as key players in the control of biological processes, and may participate in immune regulation. In this study, we investigated the molecular mechanisms in opioid-induced and miRNA-mediated immunosuppression, in the context of miRNA dysregulation in opioid abusers. Blood samples of heroin abusers were collected and analyzed using miRNA microarray analysis and quantitative PCR validation. The purified primary human monocytes were cultured in vitro to explore the underlying mechanism. We found that morphine and its derivative heroin significantly decreased the expression levels of miR-582-5p and miR-590-5p in monocytes. cAMP response element-binding protein 1 (CREB1) and CREB5 were detected as direct target genes of miR-582-5p and miR-590-5p, respectively, by using dual-luciferase assay and western bolt. Functional studies showed that knockdown of CREB1/CREB5 increased tumor necrosis factor alpha (TNF-α) level and enhanced expression of phospho-NF-κB p65 and NF-κB p65. Our results demonstrated that miR-582-5p and miR-590-5p play important roles in opioid-induced immunosuppression in monocytes by targeting CREB1/CREB5-NF-κB signaling pathway.
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Long
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Discipline of Physiology, School of Medical Sciences, the University of Adelaide, Adelaide, SA, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D015153:Blotting, Western; D016022:Case-Control Studies; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051699:Cyclic AMP Response Element-Binding Protein A / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D003932:Heroin / Q000494:pharmacology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009020:Morphine / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009293:Opioid-Related Disorders / Q000276:immunology* / Q000378:metabolism; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D051996:Transcription Factor RelA / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; C115163:CREB1 protein, human; C497102:CREB5 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D051699:Cyclic AMP Response Element-Binding Protein A; C508609:IL10 protein, human; C000593706:MIRN582 microRNA, human; C568221:MIRN590 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D010750:Phosphoproteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003932:Heroin; D009020:Morphine