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

• Published in: Inflammation 2018-12, Vol.41 (6), p.2265-2274
• Main Authors: Chen, Chien-Wei, Hu, Sindy, Tsui, Ke-Hung, Hwang, Guey-Shyang, Chen, Szu-Tah, Tang, Tswen-Kei, Cheng, Hao-Tsai, Yu, Ju-Wen, Wang, Hsiao-Chiu, Juang, Horng-Heng, Wang, Paulus S., Wang, Shyi-Wu
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; c-Jun protein; Cell cycle; Cell Cycle - drug effects; Cytokines - drug effects; Cytokines - metabolism; Cytotoxicity; Extracellular signal-regulated kinase; Flow cytometry; G2 phase; Gene expression; Gossypol; Gossypol - pharmacology; Gossypol - therapeutic use; Humans; Immunology; Inflammation; Interleukin 2; Internal Medicine; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Jurkat Cells; Kinases; Lymphocytes - drug effects; Lymphocytes - metabolism; Lymphocytes T; MAP kinase; MAP Kinase Signaling System - drug effects; Original Article; p38 Mitogen-Activated Protein Kinases - metabolism; Pathology; Pharmacology/Toxicology; Phosphorylation; Phytohemagglutinins - pharmacology; Protein kinase; Rheumatology; S phase; Signal transduction; Transcription factors
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-018-0868-6

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.