Endomorphins 1 and 2 inhibit IL-10 and IL-12 production and innate immune functions, and potentiate NF-kappaB DNA binding in THP-1 differentiated to macrophage-like cells.
We evaluated immunological effects of opioid peptides endomorphins 1 and 2 on the production of interleukin-10 (IL-10) and IL-12 cytokines, functions related to innate immunity and NF-kappaB DNA binding in human cell line THP-1. Endomorphins 1 and 2 inhibited lipopolysaccharide (LPS)-stimulated IL-10 and IL-12 production in THP-1 differentiated to macrophage-like cells by phorbol 12-myristate 13-acetate (PMA). Similarly, they suppressed LPS-stimulated IL-10 and IL-12 production in THP-1 matured to monocytes by 1alpha,25-dihydroxyvitamin D3. In addition, endomorphins 1 and 2 led to marked potentiation of NF-kappaB binding in THP-1 differentiated to macrophage-like cells. Furthermore, these endomorphins further potentiated LPS-induced NF-kappaB binding. Moreover, they inhibited chemotaxis, phagocytosis of Escherichia coli and PMA-stimulated production of hydrogen peroxide in THP-1 differentiated to macrophage-like cells. These results suggest that endomorphins 1 and 2 may inhibit THP-1 functions, such as cytokine production and functions related to innate immune, and potentiate NF-kappaB DNA binding in THP-1.
Department of Pharmacology, Osaka Dental University, Hirakata, Osaka, Japan. aazuma@cc.osaka-dent.ac.jp
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D002454:Cell Differentiation; D002460:Cell Line; D002633:Chemotaxis; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D010587:Phagocytosis; D017450:Receptors, Opioid, mu / Q000819:agonists*
D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D016753:Interleukin-10; D018664:Interleukin-12; C105294:endomorphin 2; D004247:DNA; D006861:Hydrogen Peroxide