Nat Prod Sci.  2017 Mar;23(1):1-4. 10.20307/nps.2017.23.1.1.

Sinensetin Inhibits Interleukin-6 in Human Mast Cell - 1 Via Signal Transducers and Activators of the Transcription 3 (STAT3) and Nuclear Factor Kappa B (NF-κB) Pathways

• Chae HS
• Kim YM
• Chin YW

• KMID: 2376491
• DOI: http://doi.org/10.20307/nps.2017.23.1.1

Abstract

Sinensetin, a pentamethoxyflavone, is known to exert various pharmacological activities including anti-angiogenesis, anti-diabetic and anti-inflammatory activities. However, its effects on the human mast cell - 1 (HMC-1) mediated inflammatory mechanism remain unknown. To explore the mediator and cellular inflammatory response of sinensetin, we examined its influence on phorbol 12-myristate 13-acetate (PMA) plus A23187 induced inflammatory mediator production in a human mast cell line. In this study, interleukin (IL)-6 production was measured using the enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Sinensetin inhibited PMA plus A23187 induced IL-6 production in a dose-dependent manner as well as IL-4, IL-5 and IL-8 mRNA expression. Furthermore, sinensetin inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation, suggesting that sinensetin inhibits the production of inflammatory mediators by blocking STAT3 phosphorylation. Moreover, sinensetin was found to inhibit nuclear factor kappa B activation. These findings suggest that sinensetin may be involved in the regulation of mast cell-mediated inflammatory responses.

Keyword

Sinensetin; Interleukin-6; STAT3; NF-κB

MeSH Terms

Calcimycin
Enzyme-Linked Immunosorbent Assay
Humans*
Interleukin-4
Interleukin-5
Interleukin-6*
Interleukin-8
Interleukins
Mast Cells*
NF-kappa B*
Phosphorylation
Polymerase Chain Reaction
Reverse Transcription
RNA, Messenger
STAT3 Transcription Factor
Transducers*
Calcimycin
Interleukin-4
Interleukin-5
Interleukin-6
Interleukin-8
Interleukins
NF-kappa B
RNA, Messenger
STAT3 Transcription Factor

Figure

• 

  Fig. 1 Effect of sinensetin on the release of IL-6 (A) and the expression of IL-6 mRNA (B) in PMA plus A23187-stimulated HMC-1. Statistical significance: *P < 0.05 and **P < 0.005, as compared to the PMA plus A23187 treated group. Values shown are the mean ± S.E. of duplicate determinations from three separate experiments.

• 

  Fig. 2 Effect of sinensetin on phosphorylation of STAT3 in PMA plus A23187-stimulated HMC-1. HMC-1 was pretreated with sinensetin for 0.5 h and then stimulated for 0.5 h to detect phosphorylated STAT3.

• 

  Fig. 3 Effect of sinensetin on the PMA plus A23187-induced activation of the NF-κB Pathway in HMC-1. HMC-1 was pretreated with sinensetin for 0.5 h and then stimulated for 10 min to detect cytoplasmic IκB-α, cytoplasmic p65 NF-κB and nuclear p65 NF-κB by Western blot analysis.

• 

  Fig. 4 Effect of sinensetin on the inflammatory mediators in stimulated HMC-1. HMC-1 was incubated with indicated concentration of sinensetin for 0.5 h, and then incubated with PMA plus A23187 for 6 h. mRNA level of IL-4, IL-5,and IL-8 were normalizes to that of GAPDH. *P < 0.05 and **P < 0.005, as compared to the PMA plus A23187 treated group.

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