title: Beta-estradiol-induced decrease in IL-12 and TNF-alpha expression suppresses macrophage functions in the course of Listeria monocytogenes infection in mice.
abstract: Mice treated with a contraceptive dose of beta-estradiol (E2) demonstrated changes in their macrophage (Mphi) number and functions. While E2 increased and decreased the Mphi number in PBMC and PEC respectively, it enhanced the in vitro phagocytosis of FITC-labeled beads by both cells. E2 treatment also enhanced the phagocytic function of Mphi as assessed by the in vivo carbon clearance assay. In contrast, the in vitro intracellular killing function of adherent cells in peritoneal exudate cells (PEC) against Listeria monocytogenes decreased after E2 treatment. In line with the decrease in the intracellular killing function, the E2-treated mice showed an impaired protection against L. monocytogenes infection. To clarify the mechanism of the E2-mediated suppression of the protective response against L. monocytogenes infection, we next analyzed the cytokine expression by PEC in E2-treated L. monocytogenes-infected mice. On day 5 of the infection, the expression of IL-12, TNF-alpha and IL-10 by adherent PEC from the E2-treated mice was lower than that from the control-infected mice. The decrease in the cytokine expression by adherent PEC of E2-treated mice coincided with the decrease of IFN-gamma expression, and the increase in the IL-4, IL-10 and TGF-beta expressions by non-adherent PEC. These results revealed two aspects of the effects of E2 on Mphi. Even though E2 was found to enhance Mphi phagocytosis, the anti-bacterial function was suppressed. This suppression may be mediated by the inhibition of both IL-12 and TNF-alpha which play important roles in the protective response against intracellular bacteria.
authors.affiliation: Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: M L
authors.initials: ML
authors.lastname: Salem
authors.forename: G
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: G A
authors.initials: GA
authors.lastname: Madkour
authors.forename: K
authors.initials: K
authors.lastname: Nomoto
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D007958:Leukocyte Count / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis / Q000187:drug effects; D018417:Th1 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D004958:Estradiol; D007371:Interferon-gamma