The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Heme Oxygenase-1 Modulates the Expression of Adhesion Molecules Associated with Endothelial Cell Activation
Abstract
Heme oxygenase-1 (HO-1) cleaves the porphyrin ring of heme into carbon monoxide, Fe2+, and biliverdin, which is then converted into bilirubin. Heme-derived Fe2+ induces the expression of the iron-sequestering protein ferritin and activates the ATPase Fe2+-secreting pump, which decrease intracellular free Fe2+ content. Based on the antioxidant effect of bilirubin and that of decreased free cellular Fe2+, we questioned whether HO-1 would modulate the expression of proinflammatory genes associated with endothelial cell (EC) activation. We tested this hypothesis specifically for the genes E-selectin (CD62), ICAM-1 (CD54), and VCAM-1 (CD106). We found that HO-1 overexpression in EC inhibited TNF-α-mediated E-selectin and VCAM-1, but not ICAM-1 expression, as tested at the RNA and protein level. Heme-driven HO-1 expression had similar effects to those of overexpressed HO-1. In addition, HO-1 inhibited the activation of NF-κB, a transcription factor required for TNF-α-mediated up-regulation of these genes in EC. Bilirubin and/or Fe2+ chelation mimicked the effects of HO-1, whereas biliverdin or carbon monoxide did not. In conclusion, HO-1 inhibits the expression of proinflammatory genes associated with EC activation via a mechanism that is associated with the inhibition of NF-κB activation. This effect of HO-1 is mediated by bilirubin and/or by a decrease of free intracellular Fe2+ but probably not by biliverdin or carbon monoxide.
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Cites
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Cited by
Nrf2 signaling pathway: pivotal roles in inflammation
Ahmed, S. M. U., Luo, L., Namani, A., Wang, X. J., & Tang, X. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.005 · Cited by 1,794
Mechanisms of Cell Protection by Heme Oxygenase-1
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Self-citationDissecting molecular cross-talk between Nrf2 and NF-κB response pathways
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Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential
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Sivandzade, F., Prasad, S., Bhalerao, A., & Cucullo, L. (2019) · Redox Biology · doi:10.1016/j.redox.2018.11.017 · Cited by 639
Metadata
- Authors
- Soares, M. P., Seldon, M. P., Gregoire, I. P., Vassilevskaia, T., Berberat, P. O., Yu, J., Tsui, T.-Y., & Bach, F. H.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-03
- Volume
- 172
- Issue
- 6
- Pages
- 3553-3563
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1508323668
- Cited by
- 465
- References
- 52
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- closed
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- Soares, M. P., Seldon, M. P., Gregoire, I. P., Vassilevskaia, T., Berberat, P. O., Yu, J., Tsui, T.-Y., & Bach, F. H. (2004). Heme Oxygenase-1 Modulates the Expression of Adhesion Molecules Associated with Endothelial Cell Activation. The Journal of Immunology. https://doi.org/10.4049/jimmunol.172.6.3553
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