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Hinokitiol Negatively Regulates Immune Responses through Cell Cycle Arrest in Concanavalin A-Activated Lymphocytes.

Chung CL, Leung KW, Lu WJ, Yen TL, He CF, Sheu JR, Lin KH, Lien LM - Evid Based Complement Alternat Med (2015)

Bottom Line: In addition, hinokitiol also downregulated cyclin D3, E2F1, and Cdk4 expression and upregulated p21 expression.These results revealed that hinokitiol may regulate immune responses.In addition, our findings also indicated that hinokitiol may provide benefits to treating patients with autoimmune diseases.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan ; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

ABSTRACT
Autoimmune diseases are a group of chronic inflammatory diseases that arise from inappropriate inflammatory responses. Hinokitiol, isolated from the wood of Chamaecyparis taiwanensis, engages in multiple biological activities. Although hinokitiol has been reported to inhibit inflammation, its immunological regulation in lymphocytes remains incomplete. Thus, we determined the effects of hinokitiol on concanavalin A- (ConA-) stimulated T lymphocytes from the spleens of mice. In the present study, the MTT assay revealed that hinokitiol (1-5 μM) alone did not affect cell viability of lymphocytes, but at the concentration of 5 μM it could reduce ConA-stimulated T lymphocyte proliferation. Moreover, propidium iodide (PI) staining revealed that hinokitiol arrested cell cycle of T lymphocytes at the G0/G1 phase. Hinokitiol also reduced interferon gamma (IFN-γ) secretion from ConA-activated T lymphocytes, as detected by an ELISA assay. In addition, hinokitiol also downregulated cyclin D3, E2F1, and Cdk4 expression and upregulated p21 expression. These results revealed that hinokitiol may regulate immune responses. In conclusion, we for the first time demonstrated that hinokitiol upregulates p21 expression and attenuates IFN-γ secretion in ConA-stimulated T lymphocytes, thereby arresting cell cycle at the G0/G1 phase. In addition, our findings also indicated that hinokitiol may provide benefits to treating patients with autoimmune diseases.

No MeSH data available.


Related in: MedlinePlus

Effects of hinokitiol on positive regulators of the cell cycle. Cells were treated with hinokitiol (1–5 μM) in the absence or presence of ConA (10 μg/mL) for 24 h. The specific antibodies were used to detect (a) cyclin D3, (b) Cdk4, and (c) E2F1. Data (a–c) are presented as the mean ± SEM (n = 3; **P < 0.01 and ***P < 0.001 compared with solvent control (DMSO); #P < 0.05, ##P < 0.01, and ###P < 0.001 compared with the ConA-treated group).
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fig3: Effects of hinokitiol on positive regulators of the cell cycle. Cells were treated with hinokitiol (1–5 μM) in the absence or presence of ConA (10 μg/mL) for 24 h. The specific antibodies were used to detect (a) cyclin D3, (b) Cdk4, and (c) E2F1. Data (a–c) are presented as the mean ± SEM (n = 3; **P < 0.01 and ***P < 0.001 compared with solvent control (DMSO); #P < 0.05, ##P < 0.01, and ###P < 0.001 compared with the ConA-treated group).

Mentions: The processes of cell cycling are complex and involve positive regulators such as cyclin D3, Cdk4, and E2F1 and negative regulators such as p21. These proteins were determined in this study. Our data revealed that 5 μM hinokitiol significantly inhibited ConA-induced cyclin D3 and Cdk4 expression (Figures 3(a) and 3(b)) and downregulated the transcriptional factor E2F1 (Figure 3(c)). In addition, hinokitiol upregulated the cell cycle inhibitor p21 (Figure 4(a)).


Hinokitiol Negatively Regulates Immune Responses through Cell Cycle Arrest in Concanavalin A-Activated Lymphocytes.

Chung CL, Leung KW, Lu WJ, Yen TL, He CF, Sheu JR, Lin KH, Lien LM - Evid Based Complement Alternat Med (2015)

Effects of hinokitiol on positive regulators of the cell cycle. Cells were treated with hinokitiol (1–5 μM) in the absence or presence of ConA (10 μg/mL) for 24 h. The specific antibodies were used to detect (a) cyclin D3, (b) Cdk4, and (c) E2F1. Data (a–c) are presented as the mean ± SEM (n = 3; **P < 0.01 and ***P < 0.001 compared with solvent control (DMSO); #P < 0.05, ##P < 0.01, and ###P < 0.001 compared with the ConA-treated group).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Effects of hinokitiol on positive regulators of the cell cycle. Cells were treated with hinokitiol (1–5 μM) in the absence or presence of ConA (10 μg/mL) for 24 h. The specific antibodies were used to detect (a) cyclin D3, (b) Cdk4, and (c) E2F1. Data (a–c) are presented as the mean ± SEM (n = 3; **P < 0.01 and ***P < 0.001 compared with solvent control (DMSO); #P < 0.05, ##P < 0.01, and ###P < 0.001 compared with the ConA-treated group).
Mentions: The processes of cell cycling are complex and involve positive regulators such as cyclin D3, Cdk4, and E2F1 and negative regulators such as p21. These proteins were determined in this study. Our data revealed that 5 μM hinokitiol significantly inhibited ConA-induced cyclin D3 and Cdk4 expression (Figures 3(a) and 3(b)) and downregulated the transcriptional factor E2F1 (Figure 3(c)). In addition, hinokitiol upregulated the cell cycle inhibitor p21 (Figure 4(a)).

Bottom Line: In addition, hinokitiol also downregulated cyclin D3, E2F1, and Cdk4 expression and upregulated p21 expression.These results revealed that hinokitiol may regulate immune responses.In addition, our findings also indicated that hinokitiol may provide benefits to treating patients with autoimmune diseases.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan ; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

ABSTRACT
Autoimmune diseases are a group of chronic inflammatory diseases that arise from inappropriate inflammatory responses. Hinokitiol, isolated from the wood of Chamaecyparis taiwanensis, engages in multiple biological activities. Although hinokitiol has been reported to inhibit inflammation, its immunological regulation in lymphocytes remains incomplete. Thus, we determined the effects of hinokitiol on concanavalin A- (ConA-) stimulated T lymphocytes from the spleens of mice. In the present study, the MTT assay revealed that hinokitiol (1-5 μM) alone did not affect cell viability of lymphocytes, but at the concentration of 5 μM it could reduce ConA-stimulated T lymphocyte proliferation. Moreover, propidium iodide (PI) staining revealed that hinokitiol arrested cell cycle of T lymphocytes at the G0/G1 phase. Hinokitiol also reduced interferon gamma (IFN-γ) secretion from ConA-activated T lymphocytes, as detected by an ELISA assay. In addition, hinokitiol also downregulated cyclin D3, E2F1, and Cdk4 expression and upregulated p21 expression. These results revealed that hinokitiol may regulate immune responses. In conclusion, we for the first time demonstrated that hinokitiol upregulates p21 expression and attenuates IFN-γ secretion in ConA-stimulated T lymphocytes, thereby arresting cell cycle at the G0/G1 phase. In addition, our findings also indicated that hinokitiol may provide benefits to treating patients with autoimmune diseases.

No MeSH data available.


Related in: MedlinePlus