title: Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages.
abstract: We have elucidated a putative mechanism for the host resistance against HIV-1 infection of primary human monocyte-derived macrophages (MDM) stimulated with lipopolysaccharide (LPS). We show that LPS-activated MDM both inhibited HIV-1 entry into the cells and were refractory to post-entry productive viral replication. LPS-treated cells were virtually negative for mature virions as revealed by transmission electron microscopy. LPS activation of MDM markedly enhanced the expression of heme oxygenase-1 (HO-1), a potent inducible cytoprotective enzyme. Increased HO-1 expression was accompanied by elevated production of macrophage inflammatory chemokines (MIP1α and MIP1β) by LPS-activated MDM, significantly decreased surface chemokine receptor-5 (CCR-5) expression, and substantially reduced virus replication. Treatment of cells with HO-1 inhibitor SnPP IX (tin protoporphyrin IX) attenuated the LPS-mediated responses, HIV-1 replication and secretion of MIP1α, MIP1β, and LD78β chemokines with little change in surface CCR-5 expression. These results identify a novel role for HO-1 in the modulation of host immune response against HIV infection of MDM.
authors.affiliation: Division of Monoclonal Antibodies, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Zhou
authors.forename: Namita
authors.initials: N
authors.lastname: Kumari
authors.forename: Sergei
authors.initials: S
authors.lastname: Nekhai
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Clouse
authors.forename: Larry M
authors.initials: LM
authors.lastname: Wahl
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Yamada
authors.forename: Subhash
authors.initials: S
authors.lastname: Dhawan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis / Q000378:metabolism*; D015658:HIV Infections / Q000201:enzymology / Q000276:immunology* / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000821:virology; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; D008070:Lipopolysaccharides; C493277:MAPKAP1 protein, human; D019707:Receptors, Chemokine; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1