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Proteasome inhibitors block VCAM-1 and ICAM-1 gene expression in endothelial cells without affecting nuclear translocation of nuclear factor-kappa B.
Eur J Immunol. 1996 Apr; 26(4):839-45.EJ

Abstract

Endothelial cells play a major role in recruiting leukocytes to sites of inflammation. This is accomplished, at least in part, by up-regulation of cell surface adhesion molecules, including VCAM-1 and ICAM-1, in response to cytokines. In this report, we investigated the role of the proteasome complex in mediating the interleukin (IL)- 1 beta induction of VCAM-1 and ICAM-1 gene expression in human endothelial cells. We present evidence that a proteasome inhibitor, n-acetyl-leucinyl-leucinyl-norleucinal (norLEU), as well as specific protease inhibitors, n-tosyl-Lys-chloromethylketone and N-tosyl-Phe-chloromethylketone, blocked IL-1 beta induction of VCAM-1 and ICAM-1 promoter-driven reporter gene expression in stably transfected endothelial cells. These inhibitors also blocked cytokine induced cell surface expression of VCAM-1 and ICAM-1 by human umbilical vein endothelial cells. As expected, the protease inhibitors blocked the activation of nuclear factor (NF)-kappa B in response to IL-1 beta stimulation. In contrast, norLEU did not prevent IL-1 beta-induced nuclear translocation of NF-kappa B. The effects of norLEU were specific because it did not inhibit the IL-1 beta induction of plasminogen activator inhibitor type 1 gene expression. This study demonstrates that inhibition of the proteolytic activity of the proteasome blocks IL-1 beta induction of VCAM-1 and ICAM-1 gene expression in human endothelial cells.

Authors+Show Affiliations

Biology Department, Tanabe Research Laboratories, San Diego, CA 92121, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8625976

Citation

Cobb, R R., et al. "Proteasome Inhibitors Block VCAM-1 and ICAM-1 Gene Expression in Endothelial Cells Without Affecting Nuclear Translocation of Nuclear Factor-kappa B." European Journal of Immunology, vol. 26, no. 4, 1996, pp. 839-45.
Cobb RR, Felts KA, Parry GC, et al. Proteasome inhibitors block VCAM-1 and ICAM-1 gene expression in endothelial cells without affecting nuclear translocation of nuclear factor-kappa B. Eur J Immunol. 1996;26(4):839-45.
Cobb, R. R., Felts, K. A., Parry, G. C., & Mackman, N. (1996). Proteasome inhibitors block VCAM-1 and ICAM-1 gene expression in endothelial cells without affecting nuclear translocation of nuclear factor-kappa B. European Journal of Immunology, 26(4), 839-45.
Cobb RR, et al. Proteasome Inhibitors Block VCAM-1 and ICAM-1 Gene Expression in Endothelial Cells Without Affecting Nuclear Translocation of Nuclear Factor-kappa B. Eur J Immunol. 1996;26(4):839-45. PubMed PMID: 8625976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proteasome inhibitors block VCAM-1 and ICAM-1 gene expression in endothelial cells without affecting nuclear translocation of nuclear factor-kappa B. AU - Cobb,R R, AU - Felts,K A, AU - Parry,G C, AU - Mackman,N, PY - 1996/4/1/pubmed PY - 1996/4/1/medline PY - 1996/4/1/entrez SP - 839 EP - 45 JF - European journal of immunology JO - Eur J Immunol VL - 26 IS - 4 N2 - Endothelial cells play a major role in recruiting leukocytes to sites of inflammation. This is accomplished, at least in part, by up-regulation of cell surface adhesion molecules, including VCAM-1 and ICAM-1, in response to cytokines. In this report, we investigated the role of the proteasome complex in mediating the interleukin (IL)- 1 beta induction of VCAM-1 and ICAM-1 gene expression in human endothelial cells. We present evidence that a proteasome inhibitor, n-acetyl-leucinyl-leucinyl-norleucinal (norLEU), as well as specific protease inhibitors, n-tosyl-Lys-chloromethylketone and N-tosyl-Phe-chloromethylketone, blocked IL-1 beta induction of VCAM-1 and ICAM-1 promoter-driven reporter gene expression in stably transfected endothelial cells. These inhibitors also blocked cytokine induced cell surface expression of VCAM-1 and ICAM-1 by human umbilical vein endothelial cells. As expected, the protease inhibitors blocked the activation of nuclear factor (NF)-kappa B in response to IL-1 beta stimulation. In contrast, norLEU did not prevent IL-1 beta-induced nuclear translocation of NF-kappa B. The effects of norLEU were specific because it did not inhibit the IL-1 beta induction of plasminogen activator inhibitor type 1 gene expression. This study demonstrates that inhibition of the proteolytic activity of the proteasome blocks IL-1 beta induction of VCAM-1 and ICAM-1 gene expression in human endothelial cells. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/8625976/Proteasome_inhibitors_block_VCAM_1_and_ICAM_1_gene_expression_in_endothelial_cells_without_affecting_nuclear_translocation_of_nuclear_factor_kappa_B_ L2 - https://doi.org/10.1002/eji.1830260417 DB - PRIME DP - Unbound Medicine ER -