Effects of 3-(2-Hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone (HMP) upon signalling pathways of lipopolysaccharide-induced iNOS synthesis in RAW 264.7 cells

Choi Yi Liew, Kok Wai Lam, Min Kyu Kim, Hanis H. Harith, Chau Ling Tham, Yoke Kqueen Cheah, Mohd Roslan Sulaiman, Nordin H. Lajis, Daud A. Israf

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We previously showed that 3-(2-hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone (HMP), suppressed the synthesis of various proinflammatory mediators. In this study, HMP showed a dose-dependent inhibition of NO synthesis in the RAW 264.7 murine macrophage line. The inhibition of NO synthesis was related to inhibition of p38 phosphorylation and kinase activity that led to significant inhibition of phosphorylation of ATF-2. This effect in turn caused inhibition of AP-1-DNA binding which partially explains the inhibitory effect upon the synthesis of iNOS. HMP had no effect upon phosphorylation of JNK, ERK1/2 and STAT-1. Kinase activity of JNK and ERK1/2 was also not affected by HMP as determined by levels of phosphorylated c-jun and phosphorylated elk-1. Furthermore HMP failed to block phosphorylation of IκBα, and subsequent nuclear translocation and DNA-binding activity of p65 NF-κB in IFN-γ/LPS-induced RAW 264.7 cells. Molecular docking experiments confirmed that HMP fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We conclude that the synthetic HMP is a chalcone analogue that selectively inhibits the p38/ATF-2 and AP-1 signaling pathways in the NO synthesis by the macrophage RAW 264.7.

Original languageEnglish
Pages (from-to)85-95
Number of pages11
JournalInternational Immunopharmacology
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Fingerprint

Lipopolysaccharides
Phosphorylation
Transcription Factor AP-1
Macrophages
MAP Kinase Kinase 4
Chalcone
Mitogen-Activated Protein Kinase 3
DNA
p38 Mitogen-Activated Protein Kinases
Phosphotransferases
RAW 264.7 Cells
furan
3-(2-hydroxyphenyl)-1-(5-methylfuran-2-yl)propenone

Keywords

  • Hydroxypropenone
  • iNOS
  • MAPK
  • NF-κB
  • Nitric oxide

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Effects of 3-(2-Hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone (HMP) upon signalling pathways of lipopolysaccharide-induced iNOS synthesis in RAW 264.7 cells. / Liew, Choi Yi; Lam, Kok Wai; Kim, Min Kyu; Harith, Hanis H.; Tham, Chau Ling; Cheah, Yoke Kqueen; Sulaiman, Mohd Roslan; Lajis, Nordin H.; Israf, Daud A.

In: International Immunopharmacology, Vol. 11, No. 1, 01.2011, p. 85-95.

Research output: Contribution to journalArticle

Liew, Choi Yi ; Lam, Kok Wai ; Kim, Min Kyu ; Harith, Hanis H. ; Tham, Chau Ling ; Cheah, Yoke Kqueen ; Sulaiman, Mohd Roslan ; Lajis, Nordin H. ; Israf, Daud A. / Effects of 3-(2-Hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone (HMP) upon signalling pathways of lipopolysaccharide-induced iNOS synthesis in RAW 264.7 cells. In: International Immunopharmacology. 2011 ; Vol. 11, No. 1. pp. 85-95.
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AU - Israf, Daud A.

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