Abstract |
The overactivation of macrophages causes abnormal cell death and chronic inflammatory diseases. Therefore, the modulation of macrophage-mediated cytotoxicity is expected to become a new therapeutic strategy for various inflammatory diseases. In this study, three types of short chain fatty acids ( sodium butyrate (NaB), sodium phenylbutyrate (NaPB), sodium phenylacetate (NaPA)) were found to have anti-inflammatory effects in IFN-gamma-stimulated RAW 264.7 cells. They inhibited the expression of iNOS, TNF-alpha, and IL-6 induced by IFN-gamma, while they enhanced the expression of the anti-inflammatory cytokine, IL-10. Their potency as anti-inflammatory agents was in the order of NaB>NaPB>NaPA. Further mechanistic studies revealed these three agents to repress the DNA binding and transcriptional activities of NF-kappaB, which is an important modulator of inflammation. In addition, these agents repressed the IFN-gamma-induced ERK1/2 phosphorylation without affecting the Jak/STAT activities. The potency of NF-kappaB and ERK inhibition was also in the order of NaB>NaPB>NaPA. The results suggest that the NF-kappaB and ERK signaling pathways are at least in part involved in the anti-inflammatory activities of these SCFAs. Considering that SCFAs are normally present in the body and have few side effects, they might be promising agents for the prevention and/or treatment of various inflammatory diseases.
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Authors | Jin-Sun Park, Eun-Jung Lee, Jae-Chul Lee, Won-Ki Kim, Hee-Sun Kim |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 7
Issue 1
Pg. 70-7
(Jan 2007)
ISSN: 1567-5769 [Print] Netherlands |
PMID | 17161819
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Butyrates
- Interleukin-6
- NF-kappa B
- Nitrites
- Phenylacetates
- Phenylbutyrates
- RNA, Messenger
- Tumor Necrosis Factor-alpha
- Interleukin-10
- Interferon-gamma
- Nitric Oxide Synthase Type II
- Extracellular Signal-Regulated MAP Kinases
- phenylacetic acid
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Butyrates
(pharmacology)
- Cell Line
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Interferon-gamma
- Interleukin-10
(genetics, metabolism)
- Interleukin-6
(genetics, metabolism)
- Macrophages
(drug effects, metabolism)
- Mice
- NF-kappa B
(metabolism)
- Nitric Oxide Synthase Type II
(genetics, metabolism)
- Nitrites
(metabolism)
- Phenylacetates
(pharmacology)
- Phenylbutyrates
(pharmacology)
- RNA, Messenger
(metabolism)
- Tumor Necrosis Factor-alpha
(genetics, metabolism)
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