CKBM stimulates MAPKs but inhibits LPS-induced IFN-γ in lymphocytes

Abstract

CKBM is an herbal formula composed of five Chinese medicinal herbs (Panax ginseng, Schisandra chinensis, Fructus crataegi, Ziziphus jujuba and Glycine max) supplemented with processed Saccharomyces cerevisiae. It has been demonstrated that CKBM is capable of triggering the release of IL-6 and TNFalpha from human peripheral blood mononuclear cells. In this report, T-lymphocytic Sup-T1 cells and B-lymphocytic Ramos cells were utilized as cellular models to investigate how CKBM regulates intracellular signaling as well as the production of cytokines. CKBM stimulated the three major subgroups of mitogen-activated protein kinase (i.e. ERK, JNK and p38) in Sup-T1 cells, but only triggered the activation of ERK and p38 in Ramos cells. The induction of mitogen-activated protein kinases (MAPK) activations varied with the duration of treatment, as well as with the dosage of CKBM. In terms of cytokine production, treatment of CKBM alone did not trigger the release of IL-1beta and IFNgamma, but it suppressed the LPS-induced IFNgamma production from both Sup-T1 cells and Ramos cells. In view of the therapeutic effects of traditional Chinese medicines in inflammatory and autoimmune disorders, the results suggest that CKBM may exhibit its immuno-modulatory effects by regulating intracellular signaling as well as cytokine production in different lymphocytic cell types.

KIOM-79 inhibits high glucose or AGEs-induced VEGF expression in human retinal pigment epithelial cells

“…KIOM-79 might mediate its anti-diabetic action by inhibiting the PKC-␣/␤ ␣ and p38MAPK signaling pathway, in turn inhibiting VEGF expression in human RPE cells. In contrast, Chan et al (2006) reported that a herbal formula composed of five herbs (Panax ginseng, Schianadra chinensis, Fructus crataegi, Ziziphus jujube, and Glycine max) stimulated MAPK in lymphocytes. Different components of herbs may have different chemical constitutes, mechanisms, and effects in various diseases.…”

Zizyphus lotus L. (Desf.) modulates antioxidant activity and human T-cell proliferation

“…As far as the mechanism of action of fatty acids is concerned, it has been well established that they interfere with cell signalling, particularly with the cascade of MAP kinases like ERK1/2 and p38 [42,43]. In fact, Chan et al [18] have also demonstrated that a mixture of herbs containing Zizyphus extracts also interfere with the phosphorylation of ERK1/2 and p38 in T-cells.…”

“…Adhvaryu et al [17] have shown that Zizyphus extracts alongwith other plants stimulated neutrophil functions and exerted hepatotoxic and immunomodulatory effects in guinea pigs. Chan et al [18] assessed cell signaling mechanisms in T-cells and provided the evidence that a mixture of herbs containing Zizyphus extract induced the expression of mitogen-activated protein kinases ( i.e . ERK, JNK and p38) in T-cells, indicating that the immunomodulatory effects of Zizyphus involve the activation of second messenger cascade.…”

Involvement of a Stat3 binding site in inflammation-induced enteric apelin expression

“…LPS administration in vivo increases systemic levels of numerous inflammatory cytokines, including TNF-␣, IL-1, IL-6, and IFN-␥ (4,15,40). A rise in plasma IL-6 levels was confirmed in our experiments ( Table 2).…”

“…Additionally, the influence of lipopolysaccharide (LPS) on enteric apelin expression was examined. LPS administration to rodents promotes systemic inflammation and will activate host immune and inflammatory cells, resulting in elevations of tissue and systemic levels of numerous cytokines, including TNF-␣, IL-1, IL-6, and IFN-␥ (4,15,24,33,40). The roles of the Jak/Stat signaling pathway and of a putative Stat3 binding site in the rat apelin core promoter in cytokine-and LPSinduced apelin transcriptional activity were also examined.…”