Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages

Biochem Biophys Res Commun. 2013 Jun 7;435(3):373-7. doi: 10.1016/j.bbrc.2013.04.095. Epub 2013 May 9.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Chemokines / biosynthesis
  • Chemokines / metabolism*
  • HIV Infections / enzymology
  • HIV Infections / immunology*
  • HIV Infections / prevention & control*
  • HIV-1 / immunology
  • HIV-1 / pathogenicity*
  • Heme Oxygenase-1 / biosynthesis*
  • Heme Oxygenase-1 / physiology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Lipopolysaccharides / pharmacology*
  • Macrophage Activation / immunology*
  • Macrophages / enzymology
  • Macrophages / immunology
  • Macrophages / virology
  • Receptors, Chemokine / antagonists & inhibitors*

Substances

  • Adaptor Proteins, Signal Transducing
  • Chemokines
  • Lipopolysaccharides
  • MAPKAP1 protein, human
  • Receptors, Chemokine
  • HMOX1 protein, human
  • Heme Oxygenase-1