Hypoxia-inducible factor-1alpha suppresses the expression of macrophage scavenger receptor 1

Pflugers Arch. 2009 Nov;459(1):93-103. doi: 10.1007/s00424-009-0702-y. Epub 2009 Jul 30.

Abstract

Macrophages are distributed in all peripheral tissues and play a critical role in the first line of the innate immune defenses against bacterial infection by phagocytosis of bacterial pathogens through the macrophage scavenger receptor 1 (MSR1). Within tissues, the partial pressure of oxygen (pO2) decreases depending on the distance of cells from the closest O2-supplying blood vessel. However, it is not clear how the expression of MSR1 in macrophages is regulated by low pO2. On the other hand, hypoxia-inducible factor (HIF)-1alpha is well known to control hypoxic responses through regulation of hypoxia-inducible genes. Therefore, we investigated the effects of hypoxia and HIF-1alpha on MSR1 expression and function in the macrophage cell line RAW264. Exposure to 1% O2 or treatment with the hypoxia-mimetic agent cobalt chloride (CoCl2) significantly suppressed the expression of MSR1 mRNA, accompanied by a markedly increase in levels of nuclear HIF-1alpha protein. The overexpression of HIF-1alpha in RAW264 cells suppressed the expression of MSR1 mRNA and protein, transcriptional activity of the MSR1 gene, and phagocytic capacity against the Gram-positive bacteria Listeria monocytogenes. The suppression of MSR1 mRNA by hypoxia or CoCl2 was inhibited by YC-1, an inhibitor of HIF-1alpha, or by the depletion of HIF-1alpha expression by small interference RNA. These results indicate that hypoxia transcriptionally suppresses MSR1 expression through HIF-1alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimutagenic Agents / pharmacology
  • Blotting, Western
  • Cell Hypoxia / physiology*
  • Cell Line
  • Cobalt / pharmacology
  • Gene Expression
  • Gene Expression Regulation*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oxygen
  • Partial Pressure
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scavenger Receptors, Class A / biosynthesis*
  • Transfection

Substances

  • Antimutagenic Agents
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Msr1 protein, mouse
  • RNA, Messenger
  • Scavenger Receptors, Class A
  • Cobalt
  • cobaltous chloride
  • Oxygen