| Autor: |
Tumurkhuu G; Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan., Koide N, Hiwasa T, Ookoshi M, Dagvadorj J, Abu Shadat Mohammod Noman, Iftakhar-E-Khuda I, Naiki Y, Komatsu T, Yoshida T, Yokochi T |
| Jazyk: |
angličtina |
| Zdroj: |
Innate immunity [Innate Immun] 2011 Feb; Vol. 17 (1), pp. 97-105. Date of Electronic Publication: 2009 Dec 18. |
| DOI: |
10.1177/1753425909353641 |
| Abstrakt: |
ONO 3403, a new synthetic serine protease inhibitor, is a derivative of camostat mesilate and has a higher protease-inhibitory activity. The effect of ONO 3403 on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and nitric oxide (NO) production in RAW 264.7 macrophage-like cells was examined. ONO 3403 significantly inhibited LPS-induced TNF-α production at a lower concentration than camostat mesilate. It also inhibited LPS-induced NO production. Their inhibition was responsible for the reduced mRNA expression of TNF-α and inducible NO synthase. In LPS-stimulated cells, ONO 3403 prevented the augmentation of MyD88 expression and inhibited the phosphorylation of IκB-α, stress-activated protein kinase (SAPK) and IRF-3, and the production of interferon-β. ONO 3403 abolished the elevation of the extracellular serine protease activity in response to LPS. Further, it reduced the circulating TNF-α level, hepatic injury and mortality in mice receiving an injection of D-galactosamine and LPS. ONO 3403 was suggested to inhibit LPS-induced inflammatory responses via inactivation of MyD88-dependent and independent pathways. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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