Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential - PubMed (original) (raw)

Review

. 2010 Dec 15;80(12):1895-903.

doi: 10.1016/j.bcp.2010.07.014. Epub 2010 Jul 17.

Affiliations

• PMID: 20643109
• DOI: 10.1016/j.bcp.2010.07.014

Review

Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential

Ananta Paine et al. Biochem Pharmacol. 2010.

Abstract

Heme oxygenase (HO)-1 is the inducible isoform of the first and rate-limiting enzyme of heme degradation. Induction of HO-1 protects against the cytotoxicity of oxidative stress and apoptotic cell death. More recently, HO-1 has been recognized to have major immunomodulatory and anti-inflammatory properties, which have been demonstrated in HO-1 knockout mice and a human case of genetic HO-1 deficiency. Beneficial protective effects of HO-1 in inflammation are not only mediated via enzymatic degradation of proinflammatory free heme, but also via production of the anti-inflammatory compounds bilirubin and carbon monoxide. The immunomodulatory role of HO-1 is associated with its cell type-specific functions in myeloid cells (eg. macrophages and monocytes) and in endothelial cells, as both cell types are crucially involved in the regulation of inflammatory responses. This review covers the molecular mechanisms and signaling pathways that are involved in HO-1 gene expression. In particular, it is discussed how redox-dependent transcriptional activators such as NF-E2 related factor 2 (Nrf2), NF-κB and AP-1 along with the transcription repressor BTB and CNC homologue 1 (Bach1) control the inducible HO-1 gene expression. The role of central pro- and anti-inflammatory cellular signaling cascades including p38 MAPK and phosphatidylinositol-3 kinase (PI3K)/Akt in HO-1 regulation is highlighted. Finally, emerging strategies that apply targeted pharmacological induction of HO-1 for therapeutic interventions in inflammatory conditions are summarized.

Copyright © 2010 Elsevier Inc. All rights reserved.

PubMed Disclaimer

Similar articles

• Heme oxygenase-1 and anti-inflammatory M2 macrophages.
  Naito Y, Takagi T, Higashimura Y. Naito Y, et al. Arch Biochem Biophys. 2014 Dec 15;564:83-8. doi: 10.1016/j.abb.2014.09.005. Epub 2014 Sep 18. Arch Biochem Biophys. 2014. PMID: 25241054 Review.
• Inhibition and genetic deficiency of p38 MAPK up-regulates heme oxygenase-1 gene expression via Nrf2.
  Naidu S, Vijayan V, Santoso S, Kietzmann T, Immenschuh S. Naidu S, et al. J Immunol. 2009 Jun 1;182(11):7048-57. doi: 10.4049/jimmunol.0900006. J Immunol. 2009. PMID: 19454702
• Bruton's tyrosine kinase is required for TLR-dependent heme oxygenase-1 gene activation via Nrf2 in macrophages.
  Vijayan V, Baumgart-Vogt E, Naidu S, Qian G, Immenschuh S. Vijayan V, et al. J Immunol. 2011 Jul 15;187(2):817-27. doi: 10.4049/jimmunol.1003631. Epub 2011 Jun 15. J Immunol. 2011. PMID: 21677132
• Heme oxygenase-1 and cardiovascular disease.
  Immenschuh S, Schröder H. Immenschuh S, et al. Histol Histopathol. 2006 Jun;21(6):679-85. doi: 10.14670/HH-21.679. Histol Histopathol. 2006. PMID: 16528678 Review.
• TLR4 activation alters labile heme levels to regulate BACH1 and heme oxygenase-1 expression in macrophages.
  Sudan K, Vijayan V, Madyaningrana K, Gueler F, Igarashi K, Foresti R, Motterlini R, Immenschuh S. Sudan K, et al. Free Radic Biol Med. 2019 Jun;137:131-142. doi: 10.1016/j.freeradbiomed.2019.04.024. Epub 2019 Apr 24. Free Radic Biol Med. 2019. PMID: 31026585

Cited by

• PTP1B inhibitory and anti-inflammatory effects of secondary metabolites isolated from the marine-derived fungus Penicillium sp. JF-55.
  Lee DS, Jang JH, Ko W, Kim KS, Sohn JH, Kang MS, Ahn JS, Kim YC, Oh H. Lee DS, et al. Mar Drugs. 2013 Apr 23;11(4):1409-26. doi: 10.3390/md11041409. Mar Drugs. 2013. PMID: 23612372 Free PMC article.
• Gyeji-tang water extract exerts anti-inflammatory activity through inhibition of ERK and NF-κB pathways in lipopolysaccharide-stimulated RAW 264.7 cells.
  Yoo SR, Kim Y, Lee MY, Kim OS, Seo CS, Shin HK, Jeong SJ. Yoo SR, et al. BMC Complement Altern Med. 2016 Oct 12;16(1):390. doi: 10.1186/s12906-016-1366-8. BMC Complement Altern Med. 2016. PMID: 27733198 Free PMC article.
• Nrf2 Activation Inhibits Effects of Thrombin in Human Amnion Cells and Thrombin-Induced Preterm Birth in Mice.
  Chigusa Y, Kishore AH, Mogami H, Word RA. Chigusa Y, et al. J Clin Endocrinol Metab. 2016 Jun;101(6):2612-21. doi: 10.1210/jc.2016-1059. Epub 2016 Apr 6. J Clin Endocrinol Metab. 2016. PMID: 27050800 Free PMC article.
• Menhaden oil decreases high-fat diet-induced markers of hepatic damage, steatosis, inflammation, and fibrosis in obese Ldlr-/- mice.
  Depner CM, Torres-Gonzalez M, Tripathy S, Milne G, Jump DB. Depner CM, et al. J Nutr. 2012 Aug;142(8):1495-503. doi: 10.3945/jn.112.158865. Epub 2012 Jun 27. J Nutr. 2012. PMID: 22739374 Free PMC article.
• Bursopentin (BP5) protects dendritic cells from lipopolysaccharide-induced oxidative stress for immunosuppression.
  Qin T, Yin Y, Yu Q, Yang Q. Qin T, et al. PLoS One. 2015 Feb 6;10(2):e0117477. doi: 10.1371/journal.pone.0117477. eCollection 2015. PLoS One. 2015. PMID: 25659113 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science
  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal