{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T20:44:06Z","timestamp":1781124246270,"version":"3.54.1"},"reference-count":157,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T00:00:00Z","timestamp":1609286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013928","name":"Instituto Milenio en Inmunolog\u00eda e Inmunoterapia","doi-asserted-by":"publisher","award":["P09\/016-F"],"award-info":[{"award-number":["P09\/016-F"]}],"id":[{"id":"10.13039\/501100013928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1190830"],"award-info":[{"award-number":["1190830"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","award":["I781902009"],"award-info":[{"award-number":["I781902009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u00b4s 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.<\/jats:p>","DOI":"10.3390\/ijms22010294","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T09:35:23Z","timestamp":1609320923000},"page":"294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Immune Modulation by Inhibitors of the HO System"],"prefix":"10.3390","volume":"22","author":[{"given":"Ayleen","family":"Fern\u00e1ndez-Fierro","sequence":"first","affiliation":[{"name":"Millenium Institute on Immunology and Immunotherapy, Departamento de Gen\u00e9tica Molecular y Microbiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, 8331150 Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta C.","family":"Funes","sequence":"additional","affiliation":[{"name":"Instituto Multidisciplinario de Investigaciones Biol\u00f3gicas-San Luis, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas\u2014Universidad Nacional de San Luis, 5700 San Luis, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Rios","sequence":"additional","affiliation":[{"name":"Millenium Institute on Immunology and Immunotherapy, Departamento de Gen\u00e9tica Molecular y Microbiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, 8331150 Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Covi\u00e1n","sequence":"additional","affiliation":[{"name":"Millenium Institute on Immunology and Immunotherapy, Departamento de Gen\u00e9tica Molecular y Microbiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, 8331150 Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Millenium Institute on Immunology and Immunotherapy, Departamento de Gen\u00e9tica Molecular y Microbiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, 8331150 Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis M.","family":"Kalergis","sequence":"additional","affiliation":[{"name":"Millenium Institute on Immunology and Immunotherapy, Departamento de Gen\u00e9tica Molecular y Microbiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, 8331150 Santiago, Chile"},{"name":"Departamento de Endocrinolog\u00eda, Facultad de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, 8331150 Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6388","DOI":"10.1016\/S0021-9258(18)63477-5","article-title":"Microsomal heme oxygenase. 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