Lipopolysaccharide-induced heme oxygenase-1 expression in human monocytic cells is mediated via Nrf2 and protein kinase C

Rushworth, Stuart A., Chen, Xi-Lin, Mackman, Nigel, Ogborne, Richard M. and O'Connell, Maria A. ORCID: https://orcid.org/0000-0002-0267-0951 (2005) Lipopolysaccharide-induced heme oxygenase-1 expression in human monocytic cells is mediated via Nrf2 and protein kinase C. Journal of Immunology, 175 (7). pp. 4408-4415. ISSN 0022-1767

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Abstract

Monocytes play a key role in mobilization of the immune response during sepsis. In response to LPS, monocytes produce both proinflanunatory mediators and regulatory proteins that counteract the inflammation and oxidative stress. In murine macrophages, LPS stimulates expression of heme oxygenase 1 (HO-1), a cytoprotective enzyme that catalyzes the degradation of heme. The 110-15'-untranslated region, similarly to other cytoprotective genes, contains antioxidant-response elements (AREs) that can bind the transcription factor NF-E2-related factor 2 (Nrf2). At present, the role of Nrf2 in LPS-induced HO-1 expression in monocytic cells has not been investigated. In this study, LPS induced HO-1 mRNA and protein expression in human monocytes and THP-1 cells. Nrf2 translocated from the cytosol to the nucleus in response to LPS and bound to the ARE site in the human HO-1 promoter. In addition, a dominant negative Nrf2 mutant inhibited LPS-induced HO-1 mRNA expression but not TNF-alpha mRNA expression in THP-1 cells. Ro-31-8220, a pan-protein kinase C (PKC) inhibitor, and Go6976, a classical PKC inhibitor, blunted LPS-induced HO-1 mRNA expression in monocytes and THP-1 cells. Both PKC inhibitors also blocked LPS-induced Nrf2 binding to the ARE. These results indicate that LPS-induced HO-1 expression in human monocytic cells requires Nrf2 and PKC.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Science > Research Groups > Molecular and Tissue Pharmacology Faculty of Science > Research Groups > Pharmaceutical Cell Biology (former - to 2017) Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	Rachel Smith
Date Deposited:	06 Jun 2011 15:17
Last Modified:	24 Sep 2024 09:59
URI:	https://ueaeprints.uea.ac.uk/id/eprint/31788
DOI:	10.4049/jimmunol.175.7.4408

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