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http://purl.uniprot.org/citations/21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21730055http://www.w3.org/2000/01/rdf-schema#comment"Withdrawal stress is a common occurrence in opioid users, yet very few studies have examined the effects of morphine withdrawal (MW) on immune functioning or the role of glucocorticoids in MW-induced immunomodulation. This study investigated for the first time the role of glucocorticoids in MW modulation of LPS-induced IL-12p40, a key cytokine playing a pivotal role in immunoprotection. Using WT and μ-opioid receptor knock-out mice, we show that MW in vivo significantly attenuated LPS-induced IL-12p40 mRNA and protein expression. The role of glucocorticoids in MW modulation of IL-12p40 was investigated using a murine macrophage cell line, CRL2019, in an in vitro MW model. Interestingly, MW alone in the absence of glucocorticoids resulted in a significant reduction in IL-12p40 promoter activity and mRNA and protein expression. EMSA revealed a concurrent decrease in consensus binding to transcription factors NFκB, Activator Protein-1, and CCAAT/enhancer-binding protein and Western blot analysis demonstrated a significant activation of LPS-induced ERK1/2 phosphorylation. Interestingly, although glucocorticoid treatment alone also modulated these transcription factors and ERK1/2 activation, the addition of glucocorticoids to MW samples resulted in a greater than additive reduction in the transcription factors and significant hyperactivation of LPS-induced ERK1/2 phosphorylation. ERK inhibitors reversed MW and MW plus corticosterone inhibition of LPS-induced IL-12p40. The potentiating effects of glucocorticoids were non-genomic because nuclear translocation of glucocorticoid receptor was not significantly different between MW and corticosterone treatment. This study demonstrates for the first time that MW and glucocorticoids independently modulate IL-12p40 production through a mechanism involving ERK1/2 hyperactivation and that glucocorticoids can significantly augment MW-induced inhibition of IL-12p40."xsd:string
http://purl.uniprot.org/citations/21730055http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m111.271460"xsd:string
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/author"Roy S."xsd:string
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/author"Das S."xsd:string
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/author"Barke R.A."xsd:string
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/author"Charboneau R."xsd:string
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/author"Kelschenbach J."xsd:string
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/pages"29806-29817"xsd:string
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/title"Morphine withdrawal stress modulates lipopolysaccharide-induced interleukin 12 p40 (IL-12p40) expression by activating extracellular signal-regulated kinase 1/2, which is further potentiated by glucocorticoids."xsd:string
http://purl.uniprot.org/citations/21730055http://purl.uniprot.org/core/volume"286"xsd:string
http://purl.uniprot.org/citations/21730055http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21730055
http://purl.uniprot.org/citations/21730055http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21730055
http://purl.uniprot.org/uniprot/#_A0A0R4J0Z2-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055
http://purl.uniprot.org/uniprot/#_E9Q7D3-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055
http://purl.uniprot.org/uniprot/#_E9Q7D4-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055
http://purl.uniprot.org/uniprot/#_P63085-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055
http://purl.uniprot.org/uniprot/#_A1KZZ4-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055
http://purl.uniprot.org/uniprot/#_A1KZZ6-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055
http://purl.uniprot.org/uniprot/#_A1KZZ7-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055
http://purl.uniprot.org/uniprot/#_A0A338P736-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055
http://purl.uniprot.org/uniprot/#_A0A338P781-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055
http://purl.uniprot.org/uniprot/#_A0A0U1RPX4-mappedCitation-21730055http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21730055