Prostaglandin E2 induces resistance to human immunodeficiency virus-1 infection in monocyte-derived macrophages: downregulation of CCR5 expression by cyclic adenosine monophosphate.
The chemokine receptor CCR5 can function as a coreceptor for human immunodeficiency virus-1 (HIV-1) entry into CD4(+) T cells and macrophages, especially during the early stages of HIV-1 infection. The regulation of CCR5 expression may affect not only leukocyte migration, but also infectivity by HIV-1 and, therefore, acquired immunodeficiency syndrome (AIDS) pathogenesis. We report here that agents which increase intracellular concentrations of cyclic adenosine monophosphate (cAMP) rapidly downregulate CCR5 gene expression, with consequent loss of CCR5 expression and function in monocytes/macrophages. Chemotaxis and intracellular Ca2+ mobilization in monocytes pretreated with prostaglandin E2 or dibutyryl-cAMP for 24 hours were significantly reduced in response to the CCR5 ligand, MIP-1beta. Moreover, HIV-1 entry into monocyte-derived macrophages pretreated with dibutyryl-cAMP or prostaglandin E2 was markedly decreased. Our findings suggest that resistance to HIV-1 can be induced by agents which increase cellular levels of cAMP and that this may suggest additional therapeutic strategies to limit infection by HIV-1.
Thivierge
M
M
Groupe de Recherche en Immunologie, Département de Pédiatrie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Canada.
Le Gouill
C
C
Tremblay
M J
MJ
Stanková
J
J
Rola-Pleszczynski
M
M
D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000502:physiology* / Q000821:virology*; D010120:Oxytocics / Q000494:pharmacology* / Q000627:therapeutic use; D019713:Receptors, CCR5 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014779:Virus Replication
D010120:Oxytocics; D019713:Receptors, CCR5; D000242:Cyclic AMP; D015232:Dinoprostone