Anti-inflammatory effects of short chain fatty acids in IFN-γ-stimulated RAW 264.7 murine macrophage cells: Involvement of NF-κB and ERK signaling pathways

Jin Sun Park, Eun Jung Lee, Jae Chul Lee, Won-Ki Kim, Hee Sun Kim

Research output: Contribution to journalArticle

130 Citations (Scopus)

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-γ-stimulated RAW 264.7 cells. They inhibited the expression of iNOS, TNF-α, and IL-6 induced by IFN-γ, 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-κB, which is an important modulator of inflammation. In addition, these agents repressed the IFN-γ-induced ERK1/2 phosphorylation without affecting the Jak/STAT activities. The potency of NF-κB and ERK inhibition was also in the order of NaB > NaPB > NaPA. The results suggest that the NF-κB 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.

Original languageEnglish
Pages (from-to)70-77
Number of pages8
JournalInternational Immunopharmacology
Volume7
Issue number1
DOIs
Publication statusPublished - 2007 Jan 1
Externally publishedYes

Fingerprint

MAP Kinase Signaling System
Volatile Fatty Acids
Anti-Inflammatory Agents
Macrophages
Butyric Acid
Interleukin-10
Interleukin-6
Chronic Disease
Cell Death
Phosphorylation
Cytokines
Inflammation
DNA
4-phenylbutyric acid
phenylacetic acid
Therapeutics

Keywords

  • Cytokine
  • ERK
  • iNOS
  • Macrophage
  • NF-κB
  • Short chain fatty acids

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Anti-inflammatory effects of short chain fatty acids in IFN-γ-stimulated RAW 264.7 murine macrophage cells : Involvement of NF-κB and ERK signaling pathways. / Park, Jin Sun; Lee, Eun Jung; Lee, Jae Chul; Kim, Won-Ki; Kim, Hee Sun.

In: International Immunopharmacology, Vol. 7, No. 1, 01.01.2007, p. 70-77.

Research output: Contribution to journalArticle

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