A small compound that inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production
SCIE
SCOPUS
- Title
- A small compound that inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production
- Authors
- Kim, JI; Lee, HY; Park, KS; Lee, T; Ryu, SH; Bae, YS
- Date Issued
- 2006-09-01
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Abstract
- Lipopolysaccharide (LPS) is critically involved in the inflammatory responses via generation of several pro-inflammatory cytokines. Since tumor necrosis factor-alpha (TNF-alpha) is one of the major pro-inflammatory cytokines which is induced by LPS treatment, the development of molecules capable of modulating LPS-induced TNF-alpha production is an issue of concern. We identified a novel synthetic compound that inhibits LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMCs). The active compound SM-7409 inhibited LPS-induced TNF-alpha production in a concentration-dependent manner, showing maximal activity at 5 mu M. SM-7409 inhibited LPS-induced TNF-alpha mRNA transcript accumulation and protein expression. We also found that SM-7409 strongly inhibits LPS-induced extracellular signal-regulated protein kinase activity in PBMCs. Moreover, we found that SM-7409 strongly inhibits the LPS-induced other pro-inflammatory cytokines, such as interleukin (IL)-1 beta and IL-8 in PBMCs. SM-7409 also dramatically inhibits the LPS-induced TNF-alpha production in neutrophils. Taken together, our results demonstrate that SM-7409 is a synthetic compound that inhibits LPS-induced TNF-alpha production, and thus SM-7409 should be useful for the development of chemotherapies targeting LPS-mediated inflammatory responses. (c) 2006 Elsevier Inc. All rights reserved.
- Keywords
- lipopolysaccharide; TNF-alpha; small compound; peripheral blood mononuclear cells; ERK; TOLL-LIKE RECEPTORS; INFLAMMATORY RESPONSES; ORGAN FAILURE; GRAIN DUST; CELL; IDENTIFICATION; ENDOTOXIN; DIFFERENTIATION; INHALATION; PATHWAY
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/23879
- DOI
- 10.1016/j.bbrc.2006.06.155
- ISSN
- 0006-291X
- Article Type
- Article
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 347, no. 3, page. 797 - 802, 2006-09-01
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