Involvement of Nuclear Factor-κB in the Inhibition of Pro-Inflammatory Mediators by Pinosylvin

Abstract

Nuclear factor-κB (NF-κB) is a critical transcription factor for maximal expression of many of the cytokines that are involved in the pathogenesis of inflammatory diseases. In this study, we found that pinosylvin, a natural stilbenoid that is a component of the pine leaf (Pinus densiflora), significantly inhibited LPS-induced NF-κB activation in a concentration-dependent manner. Additionally, pinosylvin was found to inhibit the LPS-induced phosphorylation and degradation of IκB α in THP-1 cells. Therefore, we have attempted to determine whether pinosylvin can inhibit the expression of cytokines possessing NF-κB binding sites in their promoter regions. In a consistent result, pinosylvin inhibited LPS-induced production of TNF α and interleukin-8 (IL-8). Taken together, these results show that pinosylvin suppresses the production of pro-inflammatory mediators through the inhibition of the NF-κB signaling pathway.

Abbreviations

LPS:Lipopolysaccharide

NF-κB:Nuclear factor-κB

COX-2:Cyclooxygenase-2

Key words

Pinosylvin - nuclear factor-κB - interleukin-8 - IκB α

References

• 1 Dziarski R, Ulmer A J, upta D. Interactions of CD14 with components of Gram-positive bacteria.  Chem Immunol. 2000;  74 83-107
• 2 Dziarski R, Ulmer A J, Gupta D. Interactions of Bacterial Lipopolysaccharide and Peptidoglycan with Mammalian CD14. In: Doyle RJ, editor Glycomicrobiology. New York; Kluwer Academic/Plenum Publishers 2000: p 145-86
• 3 Parrillo J E. Pathogenetic mechanisms of septic shock.  N Engl J Med. 1993;  328 1471-7
• 4 Bone R C. Gram-positive organisms and sepsis.  Arch Intern Med. 1994;  154 26-34
• 5 Young L S. In: Mandell GL, Bennett JE, Polin R, editors Principles and practice of infectious diseases. New York; Churchill Livingstone 1995: p 690-705
• 6 Mitchell R N, Cortran R S. In: Cortran RS, Kumar V, Collins T, editors Robbins pathologic basis of disease, 6th edition. Philadelphia; WB Saunders Co 1999: p 113-38
• 7 Janeway C A, Travers P, Walport M, Capra J D. Immunobiology, 4^th edition. London; Current Biology 1999: p 375-90
• 8 Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences.  Cell. 1986;  46 705-16
• 9 Hyers T M, Tricomi ST M, Dettenmeier P A, Fowler A A. Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome.  Am Rev Respir Dis. 1991;  144 268-71
• 10 Asahara H, Asanuma M, Ogawa N, Nishibayashi S, Inoue H. High DNA-binding activity of transcription factor NF-kappa B in synovial membranes of patients with rheumatoid arthritis.  Biochem Mol Biol Int. 1995;  37 827-32
• 11 Fang J G, Lu M, Chen Z H, Zhu H H, Li Y, Yang L. et al . Antioxidant effects of resveratrol and its analogues against the free-radical-induced peroxidation of linoleic acid in micelles.  Chemistry. 2002;  8 4191-8
• 12 Ohguchi K, Tanaka T, Kido T, Baba K, Iinuma M, Matsumoto K. et al . Effects of hydroxystilbene derivatives on tyrosinase activity.  Biochem Biophys Res Commun. 2003;  307 861-3
• 13 Pacher T, Seger C, Engelmeier D, Vajrodaya S, Hofer O, Greger H. Antifungal stilbenoids from Stemona collinsae .  J Nat Prod. 2002;  65 820-7
• 14 Park E J, Min H Y, Ahn Y H, Bae C M, Pyee J H, Lee S K. Synthesis and inhibitory effects of pinosylvin derivatives on prostaglandin E2 production in lipopolysaccharide-induced mouse macrophage cells.  Bioorg Med Chem Lett. 2004;  14 5895-8
• 15 Smith C J, Zhang Y, Kobolt C M. Pharmacological analysis of cyclooxygenase-1 in inflammation.  Proc Natl Acad Sci USA. 1998;  95 13 313-8
• 16 Wright J G, Christman J W. The role of nuclear factor kappa B in the pathogenesis of pulmonary diseases: implications for therapy.  Am J Respir Med. 2003;  2 211-9