Heme oxygenase-1: unleashing the protective properties of heme

Trends Immunol. 2003 Aug;24(8):449-55. doi: 10.1016/s1471-4906(03)00181-9.


Heme oxygenase (HO)-1 catabolizes heme into three products: carbon monoxide (CO), biliverdin (which is rapidly converted to bilirubin) and free iron (which leads to the induction of ferritin, an iron-binding protein). HO-1 serves as a "protective" gene by virtue of the anti-inflammatory, anti-apoptotic and anti-proliferative actions of one or more of these three products. Administration of CO, biliverdin, bilirubin or iron-binding compounds is protective in rodent disease models of ischemia-reperfusion injury, allograft and xenograft survival, intimal hyperplasia following balloon injury or as seen in chronic graft rejection and others. We suggest that the products of HO-1 action could be valuable therapeutic agents and speculate that HO-1 functions as a "therapeutic funnel", mediating the beneficial effects attributed to other molecules, such as interleukin-10 (IL-10), inducible nitric oxide synthase (NOS2; iNOS) and prostaglandins. This Review is the third in a series on the regulation of the immune system by metabolic pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Bilirubin / immunology
  • Bilirubin / metabolism
  • Biliverdine / immunology
  • Biliverdine / metabolism
  • Carbon Monoxide / immunology
  • Carbon Monoxide / metabolism
  • Heme / immunology
  • Heme / metabolism*
  • Heme Oxygenase (Decyclizing) / immunology*
  • Heme Oxygenase-1
  • Humans
  • Membrane Proteins
  • Protective Agents / metabolism*
  • Signal Transduction / immunology


  • Membrane Proteins
  • Protective Agents
  • Heme
  • Carbon Monoxide
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Biliverdine
  • Bilirubin