Shikonin inhibited mitogen-activated IL-4 and IL-5 production on EL-4 cells through downregulation of GATA-3 and c-Maf induction

Chen Chen Lee, Jaw Jou Kang, Bor Luen Chiang, Chien Neng Wang, Yu Wen Cheng

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Aim: To investigate the effects of shikonin on phorbol myristate acetate (PMA) plus cyclic adenosine monophosphate (cAMP)-induced T helper (T H) 2 cell cytokine production, and the underlying mechanism. Main methods: We used activated EL-4 murine T-lymphoma cells, which produce interleukin (IL)-4 and IL-5, but not interferon (IFN)-γ, as TH2 cell-like cells and treated them with PMA + cAMP to investigate the effects of shikonin on TH2 cytokines, transcriptional factors, and the related mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB signaling pathway. Key findings: The data show that shikonin inhibited the PMA + cAMP-induced mRNA and protein expression of IL-4 and IL-5 via the downregulation of GATA-binding protein-3 (GATA-3) and c-musculoaponeurotic fibrosarcoma (Maf) but not T-box expressed in T cells (T-bet). Moreover, shikonin suppressed the phosphorylation of p38, inhibitor of κB (IκB) kinase (IKK)-β and IκB-α, and the subsequent IκB-α degradation induced by PMA + cAMP; however, the PMA + cAMP-induced phosphorylation of extracellular signal-related kinase (ERK), which resulted in minor inhibition and phosphorylation of c-Jun N-terminal kinase (JNK), seemed to be unaffected by shikonin treatment. Significance: This study suggests that downregulation of GATA-3 and c-Maf via the suppression of p38, IKK-β and IκB-α phosphorylation might contribute to the inhibitory effect of shikonin on mitogen-induced IL-4 and IL-5 production in EL-4T cells. Furthermore, shikonin is a potential drug for treating allergic diseases.

Original languageEnglish
Pages (from-to)364-370
Number of pages7
JournalLife Sciences
Volume89
Issue number11-12
DOIs
Publication statusPublished - Sep 12 2011

Fingerprint

Fibrosarcoma
Interleukin-5
Mitogens
Interleukin-4
Carrier Proteins
Down-Regulation
Tetradecanoylphorbol Acetate
Phosphorylation
Cyclic AMP
Phosphotransferases
Cytokines
Th2 Cells
T-cells
JNK Mitogen-Activated Protein Kinases
T-Cell Lymphoma
shikonin
Mitogen-Activated Protein Kinases
Interferons
T-Lymphocytes
Degradation

Keywords

  • c-Maf MAPK
  • GATA-3
  • IL-4
  • Shikonin
  • T2 cells

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Shikonin inhibited mitogen-activated IL-4 and IL-5 production on EL-4 cells through downregulation of GATA-3 and c-Maf induction. / Lee, Chen Chen; Kang, Jaw Jou; Chiang, Bor Luen; Wang, Chien Neng; Cheng, Yu Wen.

In: Life Sciences, Vol. 89, No. 11-12, 12.09.2011, p. 364-370.

Research output: Contribution to journalArticle

Lee, Chen Chen ; Kang, Jaw Jou ; Chiang, Bor Luen ; Wang, Chien Neng ; Cheng, Yu Wen. / Shikonin inhibited mitogen-activated IL-4 and IL-5 production on EL-4 cells through downregulation of GATA-3 and c-Maf induction. In: Life Sciences. 2011 ; Vol. 89, No. 11-12. pp. 364-370.
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T1 - Shikonin inhibited mitogen-activated IL-4 and IL-5 production on EL-4 cells through downregulation of GATA-3 and c-Maf induction

AU - Lee, Chen Chen

AU - Kang, Jaw Jou

AU - Chiang, Bor Luen

AU - Wang, Chien Neng

AU - Cheng, Yu Wen

PY - 2011/9/12

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AB - Aim: To investigate the effects of shikonin on phorbol myristate acetate (PMA) plus cyclic adenosine monophosphate (cAMP)-induced T helper (T H) 2 cell cytokine production, and the underlying mechanism. Main methods: We used activated EL-4 murine T-lymphoma cells, which produce interleukin (IL)-4 and IL-5, but not interferon (IFN)-γ, as TH2 cell-like cells and treated them with PMA + cAMP to investigate the effects of shikonin on TH2 cytokines, transcriptional factors, and the related mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB signaling pathway. Key findings: The data show that shikonin inhibited the PMA + cAMP-induced mRNA and protein expression of IL-4 and IL-5 via the downregulation of GATA-binding protein-3 (GATA-3) and c-musculoaponeurotic fibrosarcoma (Maf) but not T-box expressed in T cells (T-bet). Moreover, shikonin suppressed the phosphorylation of p38, inhibitor of κB (IκB) kinase (IKK)-β and IκB-α, and the subsequent IκB-α degradation induced by PMA + cAMP; however, the PMA + cAMP-induced phosphorylation of extracellular signal-related kinase (ERK), which resulted in minor inhibition and phosphorylation of c-Jun N-terminal kinase (JNK), seemed to be unaffected by shikonin treatment. Significance: This study suggests that downregulation of GATA-3 and c-Maf via the suppression of p38, IKK-β and IκB-α phosphorylation might contribute to the inhibitory effect of shikonin on mitogen-induced IL-4 and IL-5 production in EL-4T cells. Furthermore, shikonin is a potential drug for treating allergic diseases.

KW - c-Maf MAPK

KW - GATA-3

KW - IL-4

KW - Shikonin

KW - T2 cells

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