Progesterone-induced inhibition of chemokine receptor expression on peripheral blood mononuclear cells correlates with reduced HIV-1 infectability in vitro.
Recent studies have shown that progesterone, a sex steroid hormone, enhances the sexual transmission of various pathogens, including SIV. The goal of this study was to determine whether progesterone affects mechanisms underlying the sexual transmission of HIV-1. We first studied the effects of various physiologic concentrations of progesterone on the expression of chemokines and chemokine receptors by T cells and macrophages. Chemokines are involved in leukocyte recruitment to peripheral sites; in addition, the chemokine receptors CCR5 and CXCR4 are HIV-1 coreceptors, and their ligands can block HIV-1 infection. Progesterone treatment had no effect on constitutive expression of CCR5 and CXCR4 by nonactivated T cells and macrophages, but significantly inhibited IL-2-induced up-regulation of CCR5 and CXCR4 on activated T cells (p < 0.05). Progesterone also inhibited both mitogen-induced proliferation and chemokine secretion (macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, RANTES) by CD8+ T lymphocytes. Control and progesterone-treated PBMC cultures were also tested for susceptibility to infection by T cell-tropic (HIV-1MN) and macrophage-tropic (HIV-1JR-CSF) viral strains in vitro. Infection with low titers of HIV-1MN was consistently inhibited in progesterone-treated cultures; progesterone effects on infection with the HIV-1JR-CSF strain were more variable, but correlated with progesterone-induced reductions in CCR5 levels. These results indicate that progesterone treatment can inhibit mechanisms underlying HIV-1 transmission, including infection of CD4+ target cells via CXCR4/CCR5 coreceptors and effects on chemokine-mediated recruitment of lymphocytes and monocytes to mucosal epithelia.
Vassiliadou
N
N
Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Tucker
L
L
Anderson
D J
DJ
D000328:Adult; D065100:CCR5 Receptor Antagonists; D002478:Cells, Cultured; D005260:Female; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D065100:CCR5 Receptor Antagonists; D007376:Interleukin-2; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011374:Progesterone