Immune Modulation by Inhibitors of the HO System
The heme oxygenase (HO) system involves three isoforms of this enzyme, HO-1, HO-2, and HO-3. The three of them display the same catalytic activity, oxidating the heme group to produce biliverdin, ferrous iron, and carbon monoxide (CO). HO-1 is the isoform most widely studied in proinflammatory disea...
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doaj-c1245f75d48d434591aedc9b10de52352020-12-31T00:01:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-012229429410.3390/ijms22010294Immune Modulation by Inhibitors of the HO SystemAyleen Fernández-Fierro0Samanta C. Funes1Mariana Rios2Camila Covián3Jorge González4Alexis M. Kalergis5Millenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, ChileInstituto Multidisciplinario de Investigaciones Biológicas-San Luis, Consejo Nacional de Investigaciones Científicas y Técnicas—Universidad Nacional de San Luis, 5700 San Luis, ArgentinaMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, ChileThe heme oxygenase (HO) system involves three isoforms of this enzyme, HO-1, HO-2, and HO-3. The three of them display the same catalytic activity, oxidating the heme group to produce biliverdin, ferrous iron, and carbon monoxide (CO). HO-1 is the isoform most widely studied in proinflammatory diseases because treatments that overexpress this enzyme promote the generation of anti-inflammatory products. However, neonatal jaundice (hyperbilirubinemia) derived from HO overexpression led to the development of inhibitors, such as those based on metaloproto- and meso-porphyrins inhibitors with competitive activity. Further, non-competitive inhibitors have also been identified, such as synthetic and natural imidazole-dioxolane-based, small synthetic molecules, inhibitors of the enzyme regulation pathway, and genetic engineering using iRNA or CRISPR cas9. Despite most of the applications of the HO inhibitors being related to metabolic diseases, the beneficial effects of these molecules in immune-mediated diseases have also emerged. Different medical implications, including cancer, Alzheimer´s disease, and infections, are discussed in this article and as to how the selective inhibition of HO isoforms may contribute to the treatment of these ailments.https://www.mdpi.com/1422-0067/22/1/294heme oxygenase-1heme oxygenase-2inhibitorsimmunomodulationinfectionscancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ayleen Fernández-Fierro Samanta C. Funes Mariana Rios Camila Covián Jorge González Alexis M. Kalergis |
spellingShingle |
Ayleen Fernández-Fierro Samanta C. Funes Mariana Rios Camila Covián Jorge González Alexis M. Kalergis Immune Modulation by Inhibitors of the HO System International Journal of Molecular Sciences heme oxygenase-1 heme oxygenase-2 inhibitors immunomodulation infections cancer |
author_facet |
Ayleen Fernández-Fierro Samanta C. Funes Mariana Rios Camila Covián Jorge González Alexis M. Kalergis |
author_sort |
Ayleen Fernández-Fierro |
title |
Immune Modulation by Inhibitors of the HO System |
title_short |
Immune Modulation by Inhibitors of the HO System |
title_full |
Immune Modulation by Inhibitors of the HO System |
title_fullStr |
Immune Modulation by Inhibitors of the HO System |
title_full_unstemmed |
Immune Modulation by Inhibitors of the HO System |
title_sort |
immune modulation by inhibitors of the ho system |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-12-01 |
description |
The heme oxygenase (HO) system involves three isoforms of this enzyme, HO-1, HO-2, and HO-3. The three of them display the same catalytic activity, oxidating the heme group to produce biliverdin, ferrous iron, and carbon monoxide (CO). HO-1 is the isoform most widely studied in proinflammatory diseases because treatments that overexpress this enzyme promote the generation of anti-inflammatory products. However, neonatal jaundice (hyperbilirubinemia) derived from HO overexpression led to the development of inhibitors, such as those based on metaloproto- and meso-porphyrins inhibitors with competitive activity. Further, non-competitive inhibitors have also been identified, such as synthetic and natural imidazole-dioxolane-based, small synthetic molecules, inhibitors of the enzyme regulation pathway, and genetic engineering using iRNA or CRISPR cas9. Despite most of the applications of the HO inhibitors being related to metabolic diseases, the beneficial effects of these molecules in immune-mediated diseases have also emerged. Different medical implications, including cancer, Alzheimer´s disease, and infections, are discussed in this article and as to how the selective inhibition of HO isoforms may contribute to the treatment of these ailments. |
topic |
heme oxygenase-1 heme oxygenase-2 inhibitors immunomodulation infections cancer |
url |
https://www.mdpi.com/1422-0067/22/1/294 |
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