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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 the cell cycle in ConA-activated T lymphocytes. Cells were treated with hinokitiol (1–5 μM) in the absence or presence of ConA (10 μg/mL) for 48 h. (a) Cell cycle was determined by PI staining under a flow cytometry. (b) The panel shows the population of the G0/G1 and S-G2/M phases. Data (b) are presented as the mean ± SEM (n = 3; **P < 0.01 compared with solvent control (DMSO); ##P < 0.01 compared with the ConA-treated group).
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fig2: Effects of hinokitiol on the cell cycle in ConA-activated T lymphocytes. Cells were treated with hinokitiol (1–5 μM) in the absence or presence of ConA (10 μg/mL) for 48 h. (a) Cell cycle was determined by PI staining under a flow cytometry. (b) The panel shows the population of the G0/G1 and S-G2/M phases. Data (b) are presented as the mean ± SEM (n = 3; **P < 0.01 compared with solvent control (DMSO); ##P < 0.01 compared with the ConA-treated group).

Mentions: PI staining was used to determine the effect of hinokitiol on the cell cycle in ConA-activated lymphocytes. Following ConA stimulation for 48 h, quiescent lymphocytes (G0) began cycling. The population of the G0/G1 phase decreased 22.9% and the population of the S and G2/M phases increased 23.1% upon ConA treatment compared with nontreatment (resting); these changes were reversed by 5 μM hinokitiol (Figures 2(a) and 2(b)). Hinokitiol markedly arrested the cell cycle at the G0/G1 phase in ConA-stimulated lymphocytes (Figure 2(a)). Compared with ConA treatment, 5 μM hinokitiol treatment increased the population of the G0/G1 phase by 24% and reduced the population of the S and G2/M phases by 25.2% (Figures 2(a) and 2(b)).


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 the cell cycle in ConA-activated T lymphocytes. Cells were treated with hinokitiol (1–5 μM) in the absence or presence of ConA (10 μg/mL) for 48 h. (a) Cell cycle was determined by PI staining under a flow cytometry. (b) The panel shows the population of the G0/G1 and S-G2/M phases. Data (b) are presented as the mean ± SEM (n = 3; **P < 0.01 compared with solvent control (DMSO); ##P < 0.01 compared with the ConA-treated group).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4563105&req=5

fig2: Effects of hinokitiol on the cell cycle in ConA-activated T lymphocytes. Cells were treated with hinokitiol (1–5 μM) in the absence or presence of ConA (10 μg/mL) for 48 h. (a) Cell cycle was determined by PI staining under a flow cytometry. (b) The panel shows the population of the G0/G1 and S-G2/M phases. Data (b) are presented as the mean ± SEM (n = 3; **P < 0.01 compared with solvent control (DMSO); ##P < 0.01 compared with the ConA-treated group).
Mentions: PI staining was used to determine the effect of hinokitiol on the cell cycle in ConA-activated lymphocytes. Following ConA stimulation for 48 h, quiescent lymphocytes (G0) began cycling. The population of the G0/G1 phase decreased 22.9% and the population of the S and G2/M phases increased 23.1% upon ConA treatment compared with nontreatment (resting); these changes were reversed by 5 μM hinokitiol (Figures 2(a) and 2(b)). Hinokitiol markedly arrested the cell cycle at the G0/G1 phase in ConA-stimulated lymphocytes (Figure 2(a)). Compared with ConA treatment, 5 μM hinokitiol treatment increased the population of the G0/G1 phase by 24% and reduced the population of the S and G2/M phases by 25.2% (Figures 2(a) and 2(b)).

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