Immunosuppressive activity of pogostone on T cells: Blocking proliferation via S phase arrest.
Pogostone (PO) is one of the major chemical constituents of the essential oil of Pogostemon cablin (Blanco) Benth. In the present study, the effect of PO on T cell responsiveness was investigated to explore its potential in immunosuppression by a Concanavalin A (ConA)-stimulation model using splenocytes isolated from C57BL/6 mice. Cytotoxicity by PO on normal splenocytes was evaluated by MTS assays. Characteristics of apoptosis, proliferation, and cell cycle were analyzed by flow cytometry. Related expressions of cyclins and cyclin-dependent kinases (CDKs) were also determined by flow cytometry. Inflammatory cytokine profiling was performed emplying cytometric beads assays (CBA). Moreover, the T cell-mediated delayed Type hepersensity (DTH) model was applied to evaluate the immunosuppressive activity of PO. Neither viability reduction in normal splenocytes nor apoptosis in ConA-stimulated splenocytes was observed under PO treatments. Meanwhile, PO remarkably reduced the total population of ConA-stimulated T cell, blocked T cell proliferation induced by Con A, and inhibited the production of IFN-γ and IL-10. This blockade of stimulated T cell proliferation by PO was likely attributed to down-regulation of cyclin E, cyclin B and CDK1 and the subsequent S-phase arrest. Additionally, PO could inhibit the DTH reaction by alleviating ear swelling and inflammatory infiltrations in the DNCB-challenged ear. Taken together, PO exhibited an immunosuppressive property by directly blocking T cell proliferation as well as altering inflammatory cytokine profile, suggesting that PO may have clinical implications for treating autoimmune diseases and other immune-based disorders.
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China; School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Ji-Yan
JY
Su
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Xia
X
Luo
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Xiao-Jun
XJ
Zhang
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Xiang-Liang
XL
Deng
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, Guangdong, 523000, China.
Zi-Ren
ZR
Su
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Lian
L
Zhou
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Shan-Shan
SS
Li
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Zhenhua
Z
Dai
The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address: yangxu@ucsd.edu.
Yang
Y
Xu
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, Guangdong, 523000, China. Electronic address: lxp88@gzucm.edu.cn.
Xiao-Ping
XP
Lai
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018836:Inflammation Mediators / Q000378:metabolism; D019686:Lamiaceae / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009822:Oils, Volatile / Q000008:administration & dosage* / Q000009:adverse effects; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D019926:Cyclin B; D019927:Cyclin E; D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D009822:Oils, Volatile; C483658:Pogostone; D016203:CDC2 Protein Kinase
Cell cycle; Immunosuppression; Pogostone; S phase arrest; T cell