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Erschienen in: Inflammation 3/2013

01.06.2013

Growth of HepG2 Cells was Suppressed Through Modulation of STAT6/IL-4 and IL-10 in RAW 264.7 Cells Treated by Phytoglycoprotein (38 kDa)

verfasst von: Jin Lee, Kye-Taek Lim

Erschienen in: Inflammation | Ausgabe 3/2013

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Abstract

Macrophage type 2 (M2) is closely associated with tumor progression and metastasis. Thus, in this study, the antitumor effect of Styrax japonica Siebold et al. Zuccarini (SJSZ) glycoprotein on HepG2 cell proliferation through modulating M2 was investigated by measuring [3H]-thymidine incorporation and proliferating cell nuclear antigen (PCNA), nitric oxide (NO), reactive oxygen species (ROS), mitogen-activated protein kinases, signal transducer and activator of transcription (STAT) 6, cytokines [interleukin (IL)-4, IL-10, IL-12, and interferon (IFN)-γ], and CD163-positive cells using biochemical analysis, radioactivity, Western blot, ELISA, quantitative real-time polymerase chain reaction, and flow cytometry in coculture system. RAW 264.7 cells were found to be cytotoxic to HepG2 cells but [3H]-thymidine incorporation and expression of PCNA was suppressed in the presence of the SJSZ glycoprotein (20 μg/ml). The SJSZ glycoprotein normalized production of NO and ROS and expression of inducible nitric oxide synthase, IFN-γ, and IL-12 but suppressed expression of pSTAT6, IL-4, IL-10, and CD163-positive cells. Thus, the results of this study suggest that the SJSZ glycoprotein suppresses proliferation of HepG2 cells by modulating M2.
Literatur
1.
Zurück zum Zitat Whiteside, T.L. 2006. Immune suppression in cancer: Effects on immune cells, mechanisms and future therapeutic intervention. Seminars in Cancer Biology 16: 3–15.PubMedCrossRef Whiteside, T.L. 2006. Immune suppression in cancer: Effects on immune cells, mechanisms and future therapeutic intervention. Seminars in Cancer Biology 16: 3–15.PubMedCrossRef
2.
Zurück zum Zitat Ince, N., and J.R. Wands. 1999. The increasing incidence of hepatocellular carcinoma. The New England Journal of Medicine 340: 798–799.PubMedCrossRef Ince, N., and J.R. Wands. 1999. The increasing incidence of hepatocellular carcinoma. The New England Journal of Medicine 340: 798–799.PubMedCrossRef
3.
Zurück zum Zitat Cabrera, R., M. Ararat, M. Ararat, M. Cao, Y. Xu, C. Wasserfall, C. Wasserfall, M.A. Atkinson, M.A. Atkinson, C. Liu, and D.R. Nelson. 2010. Hepatocellular carcinoma immunopathogenesis: Clinical evidence for global T cell defects and an immunomodulatory role for soluble CD25 (sCD25). Digestive Diseases and Sciences 55: 484–495.PubMedCrossRef Cabrera, R., M. Ararat, M. Ararat, M. Cao, Y. Xu, C. Wasserfall, C. Wasserfall, M.A. Atkinson, M.A. Atkinson, C. Liu, and D.R. Nelson. 2010. Hepatocellular carcinoma immunopathogenesis: Clinical evidence for global T cell defects and an immunomodulatory role for soluble CD25 (sCD25). Digestive Diseases and Sciences 55: 484–495.PubMedCrossRef
4.
Zurück zum Zitat Hoechst, B., L.A. Ormandy, M. Ballmaier, F. Lehner, C. Krüger, C. Krüger, M.P. Manns, T.F. Greten, and F. Korangy. 2008. A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells. Gastroenterology 135: 234–243.PubMedCrossRef Hoechst, B., L.A. Ormandy, M. Ballmaier, F. Lehner, C. Krüger, C. Krüger, M.P. Manns, T.F. Greten, and F. Korangy. 2008. A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells. Gastroenterology 135: 234–243.PubMedCrossRef
5.
Zurück zum Zitat Curiel, T.J. 2007. Tregs and rethinking cancer immunotherapy. Journal of Clinical Investigation 117: 1167–1174.PubMedCrossRef Curiel, T.J. 2007. Tregs and rethinking cancer immunotherapy. Journal of Clinical Investigation 117: 1167–1174.PubMedCrossRef
6.
Zurück zum Zitat Aderem, A., and D.M. Underhill. 1999. Mechanisms of phagocytosis in macrophages. Annual Review of Immunology 17: 593–623.PubMedCrossRef Aderem, A., and D.M. Underhill. 1999. Mechanisms of phagocytosis in macrophages. Annual Review of Immunology 17: 593–623.PubMedCrossRef
7.
Zurück zum Zitat Mantovani, A., A. Sica, S. Sozzani, P. Allavena, A. Vecchi, A. Vecchi, and M. Locati. 2004. The chemokine system in diverse forms of macrophage activation and polarization. Trends in Immunology 25: 677–686.PubMedCrossRef Mantovani, A., A. Sica, S. Sozzani, P. Allavena, A. Vecchi, A. Vecchi, and M. Locati. 2004. The chemokine system in diverse forms of macrophage activation and polarization. Trends in Immunology 25: 677–686.PubMedCrossRef
8.
Zurück zum Zitat Bingle, L., L. Bingle, N.J. Brown, and C.E. Lewis. 2001. The role of tumour-associated macrophages in tumour progression: Implications for new anticancer therapies. The Journal of Pathology 196: 254–265.CrossRef Bingle, L., L. Bingle, N.J. Brown, and C.E. Lewis. 2001. The role of tumour-associated macrophages in tumour progression: Implications for new anticancer therapies. The Journal of Pathology 196: 254–265.CrossRef
9.
Zurück zum Zitat Takai, H., M. Ashihara, T. Ishiguro, H. Terashima, T. Watanabe, A. Kato, and M. Suzuki. 2009. Involvement of glypican-3 in the recruitment of M2-polarized tumor-associated macrophages in hepatocellular carcinoma. Cancer Biology & Therapy 8: 2329–2338.CrossRef Takai, H., M. Ashihara, T. Ishiguro, H. Terashima, T. Watanabe, A. Kato, and M. Suzuki. 2009. Involvement of glypican-3 in the recruitment of M2-polarized tumor-associated macrophages in hepatocellular carcinoma. Cancer Biology & Therapy 8: 2329–2338.CrossRef
10.
Zurück zum Zitat Martinez, F.O., L. Helming, and S. Gordon. 2009. Alternative activation of macrophages: An immunologic functional perspective. Annual Review of Immunology 27: 451–483.PubMedCrossRef Martinez, F.O., L. Helming, and S. Gordon. 2009. Alternative activation of macrophages: An immunologic functional perspective. Annual Review of Immunology 27: 451–483.PubMedCrossRef
11.
Zurück zum Zitat Bafna, A.R., and S.H. Mishra. 2006. Immunostimulatory effect of methanol extract of Curculigo orchioides on immunosuppressed mice. Journal of Ethnopharmacology 104: 1–4.PubMedCrossRef Bafna, A.R., and S.H. Mishra. 2006. Immunostimulatory effect of methanol extract of Curculigo orchioides on immunosuppressed mice. Journal of Ethnopharmacology 104: 1–4.PubMedCrossRef
12.
Zurück zum Zitat Sohn, D., F. Essmann, K. Schulze-Osthoff, and R.U. Jänicke. 2006. p21 blocks irradiation-induced apoptosis downstream of mitochondria by inhibition of cyclin-dependent kinase-mediated caspase-9 activation. Cancer Research 66: 1254–11262.CrossRef Sohn, D., F. Essmann, K. Schulze-Osthoff, and R.U. Jänicke. 2006. p21 blocks irradiation-induced apoptosis downstream of mitochondria by inhibition of cyclin-dependent kinase-mediated caspase-9 activation. Cancer Research 66: 1254–11262.CrossRef
13.
Zurück zum Zitat Leary, A.G., H.Q. Zeng, S.C. Clark, M. Ogawa, and M. Ogawa. 1992. Growth factor requirements for survival in G0 and entry into the cell cycle of primitive human hemopoietic progenitors. Proceedings of the National Academy of Sciences 89: 4013–4017.CrossRef Leary, A.G., H.Q. Zeng, S.C. Clark, M. Ogawa, and M. Ogawa. 1992. Growth factor requirements for survival in G0 and entry into the cell cycle of primitive human hemopoietic progenitors. Proceedings of the National Academy of Sciences 89: 4013–4017.CrossRef
14.
Zurück zum Zitat Lee, J., and K.T. Lim. 2011. Inhibitory effect of phytoglycoprotein (38 kDa) on expression of matrix metalloproteinase-9 in 12-O-tetradecanoylphorbol-13-acetate-treated HepG2cells. Naunyn-Schmiedeberg's Archives of Pharmacology 384: 185–196.PubMedCrossRef Lee, J., and K.T. Lim. 2011. Inhibitory effect of phytoglycoprotein (38 kDa) on expression of matrix metalloproteinase-9 in 12-O-tetradecanoylphorbol-13-acetate-treated HepG2cells. Naunyn-Schmiedeberg's Archives of Pharmacology 384: 185–196.PubMedCrossRef
15.
Zurück zum Zitat Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65: 55–63.PubMedCrossRef Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65: 55–63.PubMedCrossRef
16.
Zurück zum Zitat Gabelman, B.M., and J.T. Emerman. 2002. Effects of estrogen, epidermal growth factor, and transforming growth factor-a on the growth of human breast epithelial cells in primary culture. Exp Cell Res 201: 113–118.CrossRef Gabelman, B.M., and J.T. Emerman. 2002. Effects of estrogen, epidermal growth factor, and transforming growth factor-a on the growth of human breast epithelial cells in primary culture. Exp Cell Res 201: 113–118.CrossRef
17.
Zurück zum Zitat Green, L.C., D.A. Wagner, J. Glogowski, J. Glogowski, P.L. Skipper, J.S. Wishnok, and S.R. Tannenbaum. 1982. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126: 131–138.PubMedCrossRef Green, L.C., D.A. Wagner, J. Glogowski, J. Glogowski, P.L. Skipper, J.S. Wishnok, and S.R. Tannenbaum. 1982. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126: 131–138.PubMedCrossRef
18.
Zurück zum Zitat Oh, P.S., and K.T. Lim. 2008. Plant glycoprotein modulates the expression of interleukin-1beta via inhibition of MAP kinase in HMC-1cells. Biosci Biotechnol Biochem 72: 2133–2140.PubMedCrossRef Oh, P.S., and K.T. Lim. 2008. Plant glycoprotein modulates the expression of interleukin-1beta via inhibition of MAP kinase in HMC-1cells. Biosci Biotechnol Biochem 72: 2133–2140.PubMedCrossRef
19.
Zurück zum Zitat Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275.PubMed Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275.PubMed
20.
Zurück zum Zitat Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)). Method Methods 25: 402–408.CrossRef Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)). Method Methods 25: 402–408.CrossRef
21.
Zurück zum Zitat Yu, H., D. Pardoll, and R. Jove. 2009. STATs in cancer inflammation and immunity: A leading role for STAT3. Nature Reviews Cancer 9: 798–809.PubMedCrossRef Yu, H., D. Pardoll, and R. Jove. 2009. STATs in cancer inflammation and immunity: A leading role for STAT3. Nature Reviews Cancer 9: 798–809.PubMedCrossRef
22.
Zurück zum Zitat Naderi, S., J.Y. Wang, J.Y. Wang, T.T. Chen, K.B. Gutzkow, K.B. Gutzkow, and H.K. Blomhoff. 2005. cAMP-mediated inhibition of DNA replication and S phase progression: Involvement of Rb, p21Cip1, and PCNA. Molecular Biology of the cell 16: 1527–1542.PubMedCrossRef Naderi, S., J.Y. Wang, J.Y. Wang, T.T. Chen, K.B. Gutzkow, K.B. Gutzkow, and H.K. Blomhoff. 2005. cAMP-mediated inhibition of DNA replication and S phase progression: Involvement of Rb, p21Cip1, and PCNA. Molecular Biology of the cell 16: 1527–1542.PubMedCrossRef
23.
Zurück zum Zitat Mantovani, A., and A. Sica. 2010. Macrophages, innate immunity and cancer: Balance, tolerance, and diversity. Current Opinion in Immunology 22: 31–237.CrossRef Mantovani, A., and A. Sica. 2010. Macrophages, innate immunity and cancer: Balance, tolerance, and diversity. Current Opinion in Immunology 22: 31–237.CrossRef
24.
Zurück zum Zitat Rao, K.M. 2001. MAP kinase activation in macrophages. Journal of Leukocyte Biology 69: 3–10.PubMed Rao, K.M. 2001. MAP kinase activation in macrophages. Journal of Leukocyte Biology 69: 3–10.PubMed
25.
Zurück zum Zitat David, M., D. Ford, J. Bertoglio, A.L. Maizel, and J. Pierre. 2001. Induction of the IL-13 receptor alpha2-chain by IL-4 and IL-13 in human keratinocytes: Involvement of STAT6, ERK and p38 MAPK pathways. Oncogene 20: 6660–6668.PubMedCrossRef David, M., D. Ford, J. Bertoglio, A.L. Maizel, and J. Pierre. 2001. Induction of the IL-13 receptor alpha2-chain by IL-4 and IL-13 in human keratinocytes: Involvement of STAT6, ERK and p38 MAPK pathways. Oncogene 20: 6660–6668.PubMedCrossRef
26.
Zurück zum Zitat Sinha, P., V.K. Clements, V.K. Clements, S. Miller, and S. Ostrand-Rosenberg. 2005. Tumor immunity: A balancing act between T cell activation, macrophage activation and tumor-induced immune suppression. Cancer Immunology, Immunotherapy 54: 1137–1142.PubMedCrossRef Sinha, P., V.K. Clements, V.K. Clements, S. Miller, and S. Ostrand-Rosenberg. 2005. Tumor immunity: A balancing act between T cell activation, macrophage activation and tumor-induced immune suppression. Cancer Immunology, Immunotherapy 54: 1137–1142.PubMedCrossRef
27.
Zurück zum Zitat Curiel, R.E., R. Lahesmaa, J. Subleski, M. Cippitelli, R.A. Kirken, H.A. Young, H.A. Young, and P. Ghosh. 1997. Identification of a Stat-6-responsive element in the promoter of the human interleukin-4 gene. European Journal of Immunology 27: 1982–1987.PubMedCrossRef Curiel, R.E., R. Lahesmaa, J. Subleski, M. Cippitelli, R.A. Kirken, H.A. Young, H.A. Young, and P. Ghosh. 1997. Identification of a Stat-6-responsive element in the promoter of the human interleukin-4 gene. European Journal of Immunology 27: 1982–1987.PubMedCrossRef
28.
Zurück zum Zitat Mantovani, A., S. Sozzani, M. Locati, P. Allavena, and A. Sica. 2002. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends in Immunology 23: 549–555.PubMedCrossRef Mantovani, A., S. Sozzani, M. Locati, P. Allavena, and A. Sica. 2002. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends in Immunology 23: 549–555.PubMedCrossRef
29.
Zurück zum Zitat Balkwill, F., and A. Mantovani. 2001. Inflammation and cancer: Back to Virchow? Lancet 357: 539–545.PubMedCrossRef Balkwill, F., and A. Mantovani. 2001. Inflammation and cancer: Back to Virchow? Lancet 357: 539–545.PubMedCrossRef
30.
Zurück zum Zitat Pollard, J.W. 2004. Tumour-educated macrophages promote tumour progression and metastasis. Nature Reviews Cancer 4: 71–78.PubMedCrossRef Pollard, J.W. 2004. Tumour-educated macrophages promote tumour progression and metastasis. Nature Reviews Cancer 4: 71–78.PubMedCrossRef
31.
Zurück zum Zitat Ng, I.O., E.C. Lai, S.T. Fan, M. Ng, A.S. Chan, and M.K. So. 1994. Prognostic significance of proliferating cell nuclear antigen expression in hepatocellular carcinoma. Cancer 73: 2268–2274.PubMedCrossRef Ng, I.O., E.C. Lai, S.T. Fan, M. Ng, A.S. Chan, and M.K. So. 1994. Prognostic significance of proliferating cell nuclear antigen expression in hepatocellular carcinoma. Cancer 73: 2268–2274.PubMedCrossRef
32.
Zurück zum Zitat Dunn, G.P., L.J. Old, and R.D. Schreiber. 2004. The three Es of cancer immunoediting. Annual Review of Immunology 22: 329–360.PubMedCrossRef Dunn, G.P., L.J. Old, and R.D. Schreiber. 2004. The three Es of cancer immunoediting. Annual Review of Immunology 22: 329–360.PubMedCrossRef
33.
Zurück zum Zitat Johansson, M., D.G. Denardo, and L.M. Coussens. 2008. Polarized immune responses differentially regulate cancer development. Immunological Reviews 222: 145–54.PubMedCrossRef Johansson, M., D.G. Denardo, and L.M. Coussens. 2008. Polarized immune responses differentially regulate cancer development. Immunological Reviews 222: 145–54.PubMedCrossRef
Metadaten
Titel
Growth of HepG2 Cells was Suppressed Through Modulation of STAT6/IL-4 and IL-10 in RAW 264.7 Cells Treated by Phytoglycoprotein (38 kDa)
verfasst von
Jin Lee
Kye-Taek Lim
Publikationsdatum
01.06.2013
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 3/2013
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-012-9576-9

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