A synthetic hydroxypropenone inhibits nitric oxide, prostaglandin E2, and proinflammatory cytokine synthesis

Choi Yi Liew, Chau Ling Tham, Kok Wai Lam, Azam Shah Mohamad, Min Kyu Kim, Yoke Kqueen Cheah, Zainul Amiruddin Zakaria, Mohd Roslan Sulaiman, Md Nordin Lajis, Daud Ahmad Israf

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

HMP [3-(2-hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone] was evaluated for its ability to inhibit the synthesis of major proinflammatory mediators and cytokines in interferon-γ (IFN-γ)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells and phorbol myristate acetate (PMA)- differentiated/LPS-induced U937 cells. HMP suppressed the production of nitric oxide (NO) with significant inhibitory effects at doses as low as 0.78μM (P<0.05). Prostaglandin E2 (PGE2) secretion was also inhibited at doses of 12.5μM and above (P<0.01). The secretion of both TNF-α and IL-6 were only inhibited at the highest dose used (25μM; P<0.001). IL-1β secretion was also inhibited from 12.5μM onwards (P<0.01). This inhibition was demonstrated to be caused by down-regulation of inducible enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), without direct effect upon iNOS or COX-2 enzyme activity. HMP only inhibited iNOS (P<0.001) and IL-1β (P<0.05) gene expression at the highest tested concentration. HMP did not affect the secretion of chemokines IL-8 and monocyte chemotactic protein-1 (MCP-1) and the anti-inflammatory cytokine IL-10. The most striking effect of HMP was its NO inhibitory activity and therefore we conclude that HMP is a selective inhibitor of iNOS.

Original languageEnglish
Pages (from-to)495-506
Number of pages12
JournalImmunopharmacology and Immunotoxicology
Volume32
Issue number3
DOIs
Publication statusPublished - Sep 2010
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type II
Dinoprostone
Nitric Oxide
Cytokines
Cyclooxygenase 2
Interleukin-1
Lipopolysaccharides
U937 Cells
Chemokine CCL2
Enzyme activity
Tetradecanoylphorbol Acetate
Enzymes
Interleukin-8
Chemokines
Gene expression
Interleukin-10
Interferons
Interleukin-6
Anti-Inflammatory Agents
Down-Regulation

Keywords

  • COX-2
  • Cytokines
  • Hydroxypropenone
  • INOS
  • RAW 264.7
  • U937

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology
  • Toxicology

Cite this

A synthetic hydroxypropenone inhibits nitric oxide, prostaglandin E2, and proinflammatory cytokine synthesis. / Liew, Choi Yi; Tham, Chau Ling; Lam, Kok Wai; Mohamad, Azam Shah; Kim, Min Kyu; Cheah, Yoke Kqueen; Zakaria, Zainul Amiruddin; Sulaiman, Mohd Roslan; Lajis, Md Nordin; Israf, Daud Ahmad.

In: Immunopharmacology and Immunotoxicology, Vol. 32, No. 3, 09.2010, p. 495-506.

Research output: Contribution to journalArticle

Liew, CY, Tham, CL, Lam, KW, Mohamad, AS, Kim, MK, Cheah, YK, Zakaria, ZA, Sulaiman, MR, Lajis, MN & Israf, DA 2010, 'A synthetic hydroxypropenone inhibits nitric oxide, prostaglandin E2, and proinflammatory cytokine synthesis', Immunopharmacology and Immunotoxicology, vol. 32, no. 3, pp. 495-506. https://doi.org/10.3109/08923970903575708
Liew, Choi Yi ; Tham, Chau Ling ; Lam, Kok Wai ; Mohamad, Azam Shah ; Kim, Min Kyu ; Cheah, Yoke Kqueen ; Zakaria, Zainul Amiruddin ; Sulaiman, Mohd Roslan ; Lajis, Md Nordin ; Israf, Daud Ahmad. / A synthetic hydroxypropenone inhibits nitric oxide, prostaglandin E2, and proinflammatory cytokine synthesis. In: Immunopharmacology and Immunotoxicology. 2010 ; Vol. 32, No. 3. pp. 495-506.
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AU - Mohamad, Azam Shah

AU - Kim, Min Kyu

AU - Cheah, Yoke Kqueen

AU - Zakaria, Zainul Amiruddin

AU - Sulaiman, Mohd Roslan

AU - Lajis, Md Nordin

AU - Israf, Daud Ahmad

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