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

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• 作者：Chen-Chen Lee^a ; ^b ; ^{leechenchen@mail.cmu.edu.tw"" rel=""nofollow} ; Jaw-Jou Kang^c ; Bor-Luen Chiang^d ; Chien-Neng Wang^b ; Yu-Wen Cheng^e
• 关键词：Shikonin ; T_H2 cells ; GATA-3 ; c-Maf MAPK ; IL-4
• 刊名：Life Sciences
• 出版年：2011
• 出版时间：12 September 2011
• 年：2011
• 卷：89
• 期：11-12
• 页码：364-370
• 全文大小：1103 K

文摘

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 T_H2 cell-like cells and treated them with PMA + cAMP to investigate the effects of shikonin on T_H2 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.