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

Abstract

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.