Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor α (TNF-α) in vitro. TNF-α upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-α was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-α. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-α to induce ICAM-1 expression in endothelium in vitro.
Skip Nav Destination
Article navigation
May 1998
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Research Article|
May 01 1998
Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor α in endothelium
Toshiyuki ARAI;
Toshiyuki ARAI
*Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4685, U.S.A.
Search for other works by this author on:
Susan A. KELLY;
Susan A. KELLY
*Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4685, U.S.A.
Search for other works by this author on:
Matthew L. BRENGMAN;
Matthew L. BRENGMAN
*Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4685, U.S.A.
Search for other works by this author on:
Manabu TAKANO;
Manabu TAKANO
*Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4685, U.S.A.
Search for other works by this author on:
Elise H. SMITH;
Elise H. SMITH
*Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4685, U.S.A.
Search for other works by this author on:
Pascal J. GOLDSCHMIDT-CLERMONT;
Pascal J. GOLDSCHMIDT-CLERMONT
†Department of Medicine, Ohio State University, Columbus, OH 43210-1214, U.S.A.
Search for other works by this author on:
Gregory B. BULKLEY
Gregory B. BULKLEY
1
*Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4685, U.S.A.
1To whom correspondence should be addressed.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 20 1997
Revision Received:
November 24 1997
Accepted:
December 05 1997
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 331 (3): 853–861.
Article history
Received:
August 20 1997
Revision Received:
November 24 1997
Accepted:
December 05 1997
Citation
Toshiyuki ARAI, Susan A. KELLY, Matthew L. BRENGMAN, Manabu TAKANO, Elise H. SMITH, Pascal J. GOLDSCHMIDT-CLERMONT, Gregory B. BULKLEY; Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor α in endothelium. Biochem J 1 May 1998; 331 (3): 853–861. doi: https://doi.org/10.1042/bj3310853
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.