Dual mechanisms of NF-kappaB inhibition in carnosol-treated endothelial cells

Journal Article · Sat May 15 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.01.003· OSTI ID:21344944

Lian, K -C; Chuang, J -J; Hsieh, C -W ^[1]; Huang, G -D; Jian, T -Y ^[1]; Sun, Y -W ^[2]

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1. Department of Microbiology and Immunology, National Chiayi University, Chiayi, Taiwan (China)
2. Department of Biotechnology, Seed Improvement and Propagation Station, Taichung, Taiwan (China)

The increased adhesion of monocytes to injured endothelial layers is a critical early event in atherogenesis. Under inflammatory conditions, there is increased expression of specific cell adhesion molecules on activated vascular endothelial cells, which increases monocyte adhesion. In our current study, we demonstrate a putative mechanism for the anti-inflammatory effects of carnosol, a diterpene derived from the herb rosemary. Our results show that both carnosol and rosemary essential oils inhibit the adhesion of TNFalpha-induced monocytes to endothelial cells and suppress the expression of ICAM-1 at the transcriptional level. Moreover, carnosol was found to exert its inhibitory effects by blocking the degradation of the inhibitory protein IkappaBalpha in short term pretreatments but not in 12 h pretreatments. Our data show that carnosol reduces IKK-beta phosphorylation in pretreatments of less than 3 h. In TNFalpha-treated ECs, NF-kappaB nuclear translocation and transcriptional activity was abolished by up to 12 h of carnosol pretreatment and this was blocked by Nrf-2 siRNA. The long-term inhibitory effects of carnosol thus appear to be mediated through its induction of Nrf-2-related genes. The inhibition of ICAM-1 expression and p65 translocation is reversed by HO-1 siRNA. Carnosol also upregulates the Nrf-2-related glutathione synthase gene and thereby increases the GSH levels after 9 h of exposure. Treating ECs with a GSH synthesis inhibitor, BSO, blocks the inhibitory effects of carnosol. In addition, carnosol increases p65 glutathionylation. Hence, our present findings indicate that carnosol suppresses TNFalpha-induced singling pathways through the inhibition of IKK-beta activity or the upregulation of HO-1 expression. The resulting GSH levels are dependent, however, on the length of the carnosol pretreatment period.

• OSTI ID: 21344944
• Journal Information: Toxicology and Applied Pharmacology, Vol. 245, Issue 1; Other Information: DOI: 10.1016/j.taap.2010.01.003; PII: S0041-008X(10)00014-1; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADHESION
ENDOTHELIUM
ESSENTIAL OILS
GENES
GLUTATHIONE
HERBS
INFLAMMATION
LAYERS
MONOCYTES
PHOSPHORYLATION
SYNTHESIS
TRANSLOCATION
ANIMAL TISSUES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHEMICAL REACTIONS
DRUGS
LEUKOCYTES
MATERIALS
OILS
ORGANIC COMPOUNDS
OTHER ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PEPTIDES
PLANTS
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
SYMPTOMS