THE EFFECTS OF ENDOTHELIN ON ENOTIN-INDUCED PULMONARY VASCULAR IACM-1 EXPRESSION AND ITS APPLICATION TO THE THERAPEUTIC STRATEGY OF ACUTE LUNG INJURY

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10671446
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Teikyo University
• Principal Investigator: MORITA Shigeho TEIKYO UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (60143476)
• Co-Investigator(Kenkyū-buntansha): GOTO Yukiko TEIKYO UNIVERSITY SCHOOL OF MEDICINE, STAFF ASSISTANT, 医学部, 助手 (20276710) ; TAKADA Shinji TEIKYO UNIVERSITY SCHOOL OF MEDICINE, STAFF ASSISTANT, 医学部, 助手 (90226788)
• Project Period (FY): 1998 – 1999
• Keywords: adhesion molecule / acute lung injury / endothelin / Nitric Oxide / transcriptional nuclear factor

Research Abstract

Endothelin-1 (ET-1) and Nitric Oxide (NO) play an opposing role in the control of pulmonary vascular tone. Recently, these vasoactive substances have recognized as homeostatic regulator of local vascular endothelial cells. At the site of inflammation, vascular endothelial cells are activated and endothelial-leukocyte adhesion molecules such as intercellular adhesion molecule-l (ICAM-1) are up regulated on the surface of endothelial cells.
In this project, we examined the impact of ET-1 and NO on ICAM-1 expression on cultured human pulmonary microvascular endothelial cells (HPMVEC). The results are summarized as below:
1. Under unstimulated state, neither ET-1 nor NO had any effects on ICAM-1 expression on HPMVEC.
2. NO inhibited endotoxin (LPS)-stimulated ICAM-1 expression in a dose dependent manner by 30-50% as determined by cell surface enzyme immunoassays. In contrast, ET-1 had no effect on LPS-stimulated ICAM-1 expression.
3. Immunofluorescence study indicates that the mechanism by which NO inhibits ICAM-1 expression, in part, involves inhibition of transnuclear location transcriptional nuclear factor-CB (NF-κB).
Several lines of evidence have recently suggested a role for NO as an antileukocyte autacoid. Our present study provides a link between NO and leukocyte and offers clues as to the mechanism of such an effect. We speculate development of modulatory strategies targeting NF-κB my provide a novel therapeutic tool for the treatment of lung inflammatory disease.