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

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 T(H)2 cell-like cells and treated them with PMA+cAMP to investigate the effects of shikonin on T(H)2 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.

• Authors: Chen-Chen Lee, Jaw-Jou Kang, Bor-Luen Chiang, Chien-Neng Wang, Yu-Wen Cheng
• Journal: Life sciences (Life Sci) Vol. 89 Issue 11-12 Pg. 364-70 (Sep 12 2011) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 21806999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antineoplastic Agents
• Cytokines
• Drugs, Chinese Herbal
• GATA3 Transcription Factor
• Gata3 protein, mouse
• I-kappa B Proteins
• Interleukin-5
• Maf protein, mouse
• Mitogens
• Naphthoquinones
• Proto-Oncogene Proteins c-maf
• Interleukin-4
• shikonin
• I-kappa B Kinase
• Ikbkb protein, mouse
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, toxicity)
• Antineoplastic Agents (pharmacology, toxicity)
• Cell Line, Tumor
• Cytokines (biosynthesis, genetics)
• Down-Regulation
• Drugs, Chinese Herbal (pharmacology, toxicity)
• GATA3 Transcription Factor (metabolism)
• I-kappa B Kinase (antagonists & inhibitors)
• I-kappa B Proteins (antagonists & inhibitors)
• Interleukin-4 (biosynthesis, genetics)
• Interleukin-5 (biosynthesis, genetics)
• Mice
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors)
• Mitogens (physiology)
• Naphthoquinones (pharmacology, toxicity)
• Proto-Oncogene Proteins c-maf (metabolism)
• T-Lymphocytes (drug effects, immunology)