title: Hinokitiol Negatively Regulates Immune Responses through Cell Cycle Arrest in Concanavalin A-Activated Lymphocytes.
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.
authors.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.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Chung
authors.affiliation: Department of Dentistry, Yuan's General Hospital, Kaohsiung 802, Taiwan.
authors.forename: Kam-Wing
authors.initials: KW
authors.lastname: Leung
authors.affiliation: Department of Pharmacology and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Wan-Jung
authors.initials: WJ
authors.lastname: Lu
authors.affiliation: Department of Pharmacology and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Ting-Lin
authors.initials: TL
authors.lastname: Yen
authors.affiliation: Department of Pharmacology and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Chia-Fu
authors.initials: CF
authors.lastname: He
authors.affiliation: Department of Pharmacology and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
authors.affiliation: Department of Pharmacology and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan ; Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Lin
authors.affiliation: School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan ; Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Lien