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

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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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    Authors and Affiliations

    1. Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China

      Chien-Wei Chen, Ju-Wen Yu, Hsiao-Chiu Wang & Shyi-Wu Wang

    2. Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

      Sindy Hu, Guey-Shyang Hwang & Shyi-Wu Wang

    3. Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

      Sindy Hu

    4. Department of Urology, Division of Geriatric Urology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan

      Ke-Hung Tsui

    5. Bioinformation Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

      Ke-Hung Tsui & Horng-Heng Juang

    6. Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan

      Guey-Shyang Hwang

    7. Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan

      Guey-Shyang Hwang

    8. Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan

      Szu-Tah Chen

    9. Department of Nursing, National Quemoy University, Kinmen County, Taiwan

      Tswen-Kei Tang

    10. Division of Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan

      Hao-Tsai Cheng

    11. Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

      Hao-Tsai Cheng

    12. Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan

      Horng-Heng Juang

    13. Medical Center of Aging Research, China Medical University Hospital, Taichung, Taiwan, Republic of China

      Paulus S. Wang

    14. Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan

      Paulus S. Wang

    15. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China

      Paulus S. Wang

    Author notes

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

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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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