Suppression of IL-8 gene expression by radicicol is mediated through the inhibition of ERK1/2 and p38 signaling and negative regulation of NF-κB and AP-1

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Title
Suppression of IL-8 gene expression by radicicol is mediated through the inhibition of ERK1/2 and p38 signaling and negative regulation of NF-κB and AP-1
Author(s)
Yong Ju Na; Young Jin Jeon; Jae Hong Suh; Jong Soon Kang; Kyu Hwan Yang; Hwan Mook Kim
Bibliographic Citation
International Immunopharmacology, vol. 1, no. 9, pp. 1877-1887
Publication Year
2001
Abstract
We show that radicicol, an anti-fungal agent, inhibits interleukin-8 (IL-8) production by the human monocyte line THP-1 in response to phorbol-12-myristate-13-acetate/lipopolysaccharide (PMA/LPS). IL-8 is a potent chemokine and needs for an optimal immune response - such as inflammation by activation of neutrophils. The decrease in PMA/LPS-induced IL-8 mRNA expression was demonstrated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Since the promoter in IL-8 gene contains binding motifs for NF-κB, AP-1, and NF-IL6, which appear to be important in IL-8 induction, the effects of radicicol on the activation of these transcription factors were examined. Treatment of radicicol to THP-1 cells produced a strong inhibition of NF-κB and AP-1, while NF-IL6 was not significantly affected by radicicol. Western blot analysis showed that radicicol inhibited the phosphorylation and phosphotransferase activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38. PD98059 and SB203580, known as a specific inhibitor of MEK1 and p38 kinase, respectively, inhibited IL-8 gene expression showing that both of the kinase pathways are involved in IL-8 regulation in human monocytes. Collectively, this series of experiments indicates that radicicol inhibits IL-8 gene expression by blocking ERK1/2 and p38 signaling.
Keyword
radicicolinterleukin-8ERK1/2P38NF-κBAP-1
ISSN
1567-5769
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/S1567-5769(01)00113-8
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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