Korean J Physiol Pharmacol.  2004 Oct;8(5):273-280.

Inhibition of Inducible Nitric Oxide Synthase Expression by YS 49, a Synthetic Isoquinoline Alkaloid, in ROS 17/2.8 Cells Activated with TNF-alpha, IFN-gamma and LPS

• Kang YJ
• Kang SY
• Lee YS
• Park MK
• Kim HJ
• Seo HG
• Lee JH
• Yun-Choi H
• Chang KC

Abstract

Nitric oxide (NO) has been suggested to act as a mediator of cytokine-induced effects of turn over of bone. Activation of the inducible nitric oxide synthase (iNOS) by inflammation has been related with apoptotic cell death in osteoblast. YS 49, a synthetic isoquinoline alkaloid, inhibits NO production in macrophages activated with cytokines. In the present study, we investigated the molecular mechanism of YS 49 to inhibit iNOS expression in ROS 17/2.8 cells, which were activated with combined treatment of inflammatory cytokines (TNF-alpha, IFN-gamma) and lipopolysaccharide (LPS). Results indicated that YS 49 concentration-dependently reduced iNOS mRNA and protein expression, as evidenced by Northern and Western blot analysis, respectively. The underlying mechanism by which YS 49 suppressed iNOS expression was not to affect iNOS mRNA stability but to inhibit activation and translocation of NF-kappaB by preventing the degradation of its inhibitory protein IkappaBalpha. As expected, YS 49 prevented NO-induced apoptotic cell death by sodium nitroprusside. Taken together, it is concluded that YS 49 inhibits iNOS expression by interfering with degradation of phosphorylated inhibitory kappaBalpha (p-IkappaBalpha). These actions may be beneficial for the treatment of inflammation of the joint, such as rheumatoid arthritis.

Keyword

Tetrahydroisoquinoline; Inducible nitric oxide synthase; Osteoblast; Nuclear kappa B; Cytokines

MeSH Terms

Arthritis, Rheumatoid
Blotting, Western
Cell Death
Cytokines
Inflammation
Joints
Macrophages
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type II*
Nitroprusside
Osteoblasts
RNA Stability
RNA, Messenger
Tumor Necrosis Factor-alpha*
Cytokines
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type II
Nitroprusside
RNA, Messenger
Tumor Necrosis Factor-alpha