THI 52 Inhibits Inducible Nitric Oxide Synthase Gene Expression in RAW 264.7 Cells and Rat Lung Tissue by Lipopolysaccharide

• 영문명: THI 52 Inhibits Inducible Nitric Oxide Synthase Gene Expression in RAW 264.7 Cells and Rat Lung Tissue by Lipopolysaccharide
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Bog Kyu Lee Min Kyu Park Han Geuk Seo Hye Sook Yun-Choi Duck Hyung Lee Ki Churl Chang
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제5권 제5호, 443~449쪽, 전체 7쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2001.01.01

영문 초록

Previously we reported that THI 52 inhibits tumor necrosis factor (TNF)-α mRNA expression in mouse peritoneal macrophages exposed to LPS plus IFN-γ. In the present study, the effects of THI 52 on vascular reactivity ex vivo, and iNOS protein expression (rat lung) were investigated in LPS-treated rats. Treatment of THI 52 concentration-dependently reduced not only serum nitrite production but also the expression of iNOS protein in rat lung tissues. Thoracic aorta taken from LPS injected rat for 8 h ex vivo resulted in suppression of vasoconstrictor effects to phenylephrine (PE), which was restored by THI 52 (20 mg/kg) 30 min prior to LPS. When measured iNOS activity, treatment of THI 52 concentration-dependently reduced the enzyme activity in RAW 264.7 cells activated with LPS plus IFN-γ. Likewise, iNOS activity was significantly reduced in lung tissues taken those rats that were injected THI 52 prior to LPS injection compared with LPS injection alone. These results strongly suggest that THI 52 can suppress iNOS gene expression induced by LPS, and restore the vascular contractility to PE. Thus, THI 52, a new synthetic isoquinoline alkaloid, may be beneficial in inflammatory disorders where production of NO is excessed by iNOS expression.

키워드

Nitric oxide Inducible nitric oxide synthase LPS NF-ĸ B Septic shock