Suppression of iNOS Expression by NSAIDs and Acetaminophen in Vascular Smooth Muscle Cells.
- Author:
Hyun Jin JO
1
;
Hyoung Chul CHOI
;
Kwang Youn LEE
;
Jeoung Hee HA
;
Hae Chang JO
Author Information
1. Department of Pharmacology, College of Medicine, Yeungnam University, Korea.hcchoi@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
LPS;
iNOS;
NSAIDs;
Acetaminophen
- MeSH:
Acetaminophen*;
Animals;
Anti-Inflammatory Agents, Non-Steroidal*;
Aorta;
Aspirin;
Blotting, Western;
Culture Media;
Glucocorticoids;
Immunohistochemistry;
Immunosuppression;
Indomethacin;
Ketoprofen;
Multiple Organ Failure;
Muscle, Smooth, Vascular*;
Myosins;
Rats;
RNA, Messenger;
Shock, Septic;
Sodium Salicylate;
Spectrophotometry
- From:Journal of the Korean Society for Vascular Surgery
2004;20(1):24-29
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: iNOS expression in vascular smooth muscle cells (VSMC) causes the development of septic shock, and multiple organ dysfunction syndrome (MODS). For the inhibition of iNOS expression, glucocorticoids are known to inhibit iNOS expression but immunosuppression decreases its clinical availability. Recently, aspirin was reported to inhibit iNOS expression, but the mechanism and effectiveness are still unclear. In this investigation, on aspirin, several non steroidal antiinflammatory drugs (NSAIDs) were applied to clarify the inhibitory mechanism of iNOS expression and NO production in lipopolysaccharide (LPS) treated VSMCs. METHOD: VSMCs were primarily cultured from rat aorta and confirmed by immunocytochemistry of anti-smooth muscle myosin antibody. LPS, an inducer of iNOS, and NSAIDs, such as aspirin, indomethacin, ketoprofen sodium salicylate and acetaminophen were used. The concentrations of nitrite in culture media following the addition of LPS with a 1-hour pretreatment of NSAIDs were measured by spectrophotometry with griess reaction. Western blot and RT-PCR for iNOS protein and iNOS mRNA, respectively, were performed. RESULT: Acetaminophen had no effect on the inhibition of nitrite production. NSAIDs, especially ketoprofen and sodium salicylate, showed a significant inhibitory effect on nitrite production. In their mechanism, all the NSAIDs in present study inhibited iNOS mRNA and protein expression. CONCLUSION: These results suggest that the inhibitory mechanism on iNOS expression of NSAIDs is due to the inhibition of iNOS mRNA expression and subsequent inhibition of iNOS protein expression.
