title: Immuno-regulatory effects of CKBM on the activities of mitogen-activated protein kinases and the release of cytokines in THP-1 monocytic cells.
abstract: CKBM is an herbal formula composed of five Chinese medicinal herbs (Panax ginseng, Schisandra chinensis, Fructus crataegi, Ziziphus jujube and Glycine Max) supplemented with processed Saccharomyces cerevisiae. Previous studies have demonstrated that CKBM is capable of triggering the release of IL-6 and TNFalpha from human peripheral blood mononuclear cells, and its anti-tumorigenic activity has been demonstrated in nude mice with gastric cancer. In this report, we utilized the THP-1 monocytic cell line as a cellular model to investigate how CKBM regulates the intracellular signaling of monocytes and the subsequent release of the produced cytokines. In terms of mitogen-activated protein kinase (MAPK) cascades, CKBM (20%) had no significant effect on ERK, but was linked to an inhibitory effect on JNK and a stimulatory effect on p38 MAPK. The differential responsiveness of JNK and p38 was dependent on the duration of treatment, as well as on the dosage of CKBM. Treatment of CKBM alone induced the release of IL-10 and IFNgamma, but not IL-1beta, IL-4, IL-6 and TNFbeta, while increase of intracellular Ca2+ concentration by A23187 triggered the release of IL-10 only. Interestingly, A23187 synergized with the activities of CKBM-treated THP-1 cells in terms of IL-1beta and IFNgamma production, while the IL-10 production showed no synergistic relationship between CKBM and A23187. This A23187-induced synergism was associated with a dose-dependent character towards CKBM administration. In view of the intracellular Ca2+ elevation during monocyte activation, our results suggest that CKBM can serve as a promoting agent for modulating the functions of monocytes.
authors.affiliation: Department of Biochemistry, Molecular Neuroscience Center and Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Anthony Siu Lung
authors.initials: AS
authors.lastname: Chan
authors.forename: Eric Chun-Hung
authors.initials: EC
authors.lastname: Yip
authors.forename: Lisa Ying
authors.initials: LY
authors.lastname: Yung
authors.forename: Haihong
authors.initials: H
authors.lastname: Pang
authors.forename: Sharon Chui-Wah
authors.initials: SC
authors.lastname: Luk
authors.forename: Shiu Fun
authors.initials: SF
authors.lastname: Pang
authors.forename: Yung Hou
authors.initials: YH
authors.lastname: Wong
mesh_terms: D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007155:Immunologic Factors; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000502:physiology
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D007155:Immunologic Factors; D007476:Ionophores; D016328:NF-kappa B; D015534:Trans-Activators; D016753:Interleukin-10; D000001:Calcimycin; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases