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The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells.

Wang LC, Lin YL, Liang YC, Yang YH, Lee JH, Yu HH, Wu WM, Chiang BL - BMC Immunol. (2009)

Bottom Line: CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS) and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract.CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract.These results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-kappaB signaling pathway.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei 100, Taiwan, Republic of China.lcwang5@ntu.edu.tw

ABSTRACT

Background: Propolis, an ancient herbal medicine, has been reported the beneficial effect both in asthma patients and murine model of asthma, but the mechanism was not clearly understood. In this study, the effect of caffeic acid phenethyl ester (CAPE), the most extensively studied components in propolis, on the functions of human monocyte-derived dendritic cells (MoDCs) was investigated.

Results: CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS) and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract. CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract. In contrast, the upregulation of costimulatory molecules in mature MoDCs was not suppressed by CAPE. Further, the antigen presenting ability of DCs was not inhibited by CAPE. CAPE inhibited IkappaBalpha phosphorylation and NF-kappaB activation but not mitogen-activated protein kinase (MAPK) family phosphorylation in human MoDCs.

Conclusion: These results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-kappaB signaling pathway. This study provided a new insight into the mechanism of CAPE in immune response and the rationale for propolis in the treatment of asthma and other allergic disorders.

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The effect of CAPE-treated MoDCs on T cell activation. Mature MoDCs (105 cells/mL) from eight non-atopic healthy subjects and four mite-sensitized allergic patients treated as indicated were co-cultured with autologous naïve CD4+ T cells (106 cells/mL). (A) Supernatants were analyzed for IFN-γ and IL-5, which were produced by activated T cells after 3 days of culture. (B) Tritiated(3H) thymidine incorporation was measured by liquid scintillation counting after 5 days of culture and expressed as mean counts per minute (cpm). *P < 0.05; **P < 0.01.
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Figure 4: The effect of CAPE-treated MoDCs on T cell activation. Mature MoDCs (105 cells/mL) from eight non-atopic healthy subjects and four mite-sensitized allergic patients treated as indicated were co-cultured with autologous naïve CD4+ T cells (106 cells/mL). (A) Supernatants were analyzed for IFN-γ and IL-5, which were produced by activated T cells after 3 days of culture. (B) Tritiated(3H) thymidine incorporation was measured by liquid scintillation counting after 5 days of culture and expressed as mean counts per minute (cpm). *P < 0.05; **P < 0.01.

Mentions: Mature DCs have the capacity to induce proliferation and cytokine production in T cells [27]. In the present study, autologous naïve CD4+ T cells was employed in an activation assay to determine if CAPE treated MoDCs have a decreased ability to activate T cells. The treated MoDCs were co-cultured with autologous naïve CD4+ T cells for 3 days in the ratio of 1:10. LPS-pulsed MoDCs induced T cells to secrete IFN-γ compared to controls MoDCs (P = 0.023) in healthy subjects (Figure 4A). Crude mite extract-pulsed MoDCs induced T cells to secrete large amount of IFN-γ and IL-5 (P = 0.013, < 0.001, respectively) and higher lymphoproliferation (P = 0.002) compared to control MoDCs (Figure 4B). In allergic patients, LPS-pulsed MoDCs and crude mite extract-pulsed MoDCs induced higher T cell lymphoproliferation than control MoDCs (P = 0.039, 0.008, respectively). IFN-γ secretion by T cells co-cultured with LPS or crude mite extract stimulated MoDCs was higher in healthy subjects than in allergic patients (P = 0.015, 0.012, respectively). There was no difference in T cell cytokine production (IFN-γ and IL-5) and lymphoproliferation between MoDCs that were or were not treated with CAPE in both healthy subjects and allergic patients (Figure 4A and 4B).


The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells.

Wang LC, Lin YL, Liang YC, Yang YH, Lee JH, Yu HH, Wu WM, Chiang BL - BMC Immunol. (2009)

The effect of CAPE-treated MoDCs on T cell activation. Mature MoDCs (105 cells/mL) from eight non-atopic healthy subjects and four mite-sensitized allergic patients treated as indicated were co-cultured with autologous naïve CD4+ T cells (106 cells/mL). (A) Supernatants were analyzed for IFN-γ and IL-5, which were produced by activated T cells after 3 days of culture. (B) Tritiated(3H) thymidine incorporation was measured by liquid scintillation counting after 5 days of culture and expressed as mean counts per minute (cpm). *P < 0.05; **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2724478&req=5

Figure 4: The effect of CAPE-treated MoDCs on T cell activation. Mature MoDCs (105 cells/mL) from eight non-atopic healthy subjects and four mite-sensitized allergic patients treated as indicated were co-cultured with autologous naïve CD4+ T cells (106 cells/mL). (A) Supernatants were analyzed for IFN-γ and IL-5, which were produced by activated T cells after 3 days of culture. (B) Tritiated(3H) thymidine incorporation was measured by liquid scintillation counting after 5 days of culture and expressed as mean counts per minute (cpm). *P < 0.05; **P < 0.01.
Mentions: Mature DCs have the capacity to induce proliferation and cytokine production in T cells [27]. In the present study, autologous naïve CD4+ T cells was employed in an activation assay to determine if CAPE treated MoDCs have a decreased ability to activate T cells. The treated MoDCs were co-cultured with autologous naïve CD4+ T cells for 3 days in the ratio of 1:10. LPS-pulsed MoDCs induced T cells to secrete IFN-γ compared to controls MoDCs (P = 0.023) in healthy subjects (Figure 4A). Crude mite extract-pulsed MoDCs induced T cells to secrete large amount of IFN-γ and IL-5 (P = 0.013, < 0.001, respectively) and higher lymphoproliferation (P = 0.002) compared to control MoDCs (Figure 4B). In allergic patients, LPS-pulsed MoDCs and crude mite extract-pulsed MoDCs induced higher T cell lymphoproliferation than control MoDCs (P = 0.039, 0.008, respectively). IFN-γ secretion by T cells co-cultured with LPS or crude mite extract stimulated MoDCs was higher in healthy subjects than in allergic patients (P = 0.015, 0.012, respectively). There was no difference in T cell cytokine production (IFN-γ and IL-5) and lymphoproliferation between MoDCs that were or were not treated with CAPE in both healthy subjects and allergic patients (Figure 4A and 4B).

Bottom Line: CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS) and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract.CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract.These results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-kappaB signaling pathway.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei 100, Taiwan, Republic of China.lcwang5@ntu.edu.tw

ABSTRACT

Background: Propolis, an ancient herbal medicine, has been reported the beneficial effect both in asthma patients and murine model of asthma, but the mechanism was not clearly understood. In this study, the effect of caffeic acid phenethyl ester (CAPE), the most extensively studied components in propolis, on the functions of human monocyte-derived dendritic cells (MoDCs) was investigated.

Results: CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS) and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract. CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract. In contrast, the upregulation of costimulatory molecules in mature MoDCs was not suppressed by CAPE. Further, the antigen presenting ability of DCs was not inhibited by CAPE. CAPE inhibited IkappaBalpha phosphorylation and NF-kappaB activation but not mitogen-activated protein kinase (MAPK) family phosphorylation in human MoDCs.

Conclusion: These results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-kappaB signaling pathway. This study provided a new insight into the mechanism of CAPE in immune response and the rationale for propolis in the treatment of asthma and other allergic disorders.

Show MeSH
Related in: MedlinePlus