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Anti-inflammatory Effects of Gossypol on Human Lymphocytic Jurkat Cells via Regulation of MAPK Signaling and Cell Cycle

Abstract

Gossypol, a natural polyphenolic compound extracted from cottonseed oil, has been reported to possess pharmacological properties via modulation cell cycle and immune signaling pathway. However, whether gossypol has anti-inflammatory effects against phytohemagglutinin (PHA)-induced cytokine secretion in T lymphocytes through similar mechanism remains unclear. Using the T lymphocytes Jurkat cell line, we found that PHA exposure caused dramatic increase in interleukin-2 (IL-2) mRNA expression as well as IL-2 secretion. All of these PHA-stimulated reactions were attenuated in a dose-dependent manner by being pretreated with gossypol. However, gossypol did not show any in vitro cytotoxic effect at doses of 5–20 μM. As a possible mechanism underlying gossypol action, such as pronounced suppression IL-2 release, robust decreased PHA-induced phosphorylation of p38 and c-Jun N-terminal kinase expressions was found with gossypol pretreatment, but not significant phosphorylation of extracellular signal-regulated kinase expression. Furthermore, gossypol could suppress the Jurkat cells’ growth, which was associated with increased percentage of G1/S phase and decreased fraction of G2 phase in flow cytometry test. We conclude that gossypol exerts anti-inflammatory effects probably through partial attenuation of mitogen-activated protein kinase (phosphorylated JNK and p38) signaling and cell cycle arrest in Jurkat cells.

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Acknowledgments

The English editing provided by Miss Jennifer S. Wang is appreciated.

Funding

The authors were financially supported in part by grants CMRPD1C0491, CMRPD1C0492, CMRPG5D0071, CMRPG5R0011, CMRPD3E0042, CMRPG3F080 (1-3), and CMRPG3E015 (1-3) from Chang Gung Memorial Hospital Foundation, Taiwan, ROC.

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  1. Chien-Wei Chen and Sindy Hu contributed equally to this work.

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    Correspondence to Paulus S. Wang or Shyi-Wu Wang.

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    Chen, CW., Hu, S., Tsui, KH. et al. Anti-inflammatory Effects of Gossypol on Human Lymphocytic Jurkat Cells via Regulation of MAPK Signaling and Cell Cycle. Inflammation 41, 2265–2274 (2018). https://doi.org/10.1007/s10753-018-0868-6

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    KEY WORDS

    • cell cycle
    • gossypol
    • interleukin-2
    • Jurkat cell
    • mitogen-activated protein kinase