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Paeoniflorin attenuates schistosomiasis japonica-associated liver fibrosis through inhibiting alternative activation of macrophages

Published online by Cambridge University Press:  03 August 2011

DEYONG CHU ,
MINGZHAN DU ,
XIANGYANG HU ,
QIANG WU  and
JILONG SHEN
DEYONG CHU
Affiliation:
Department of Microbiology and Parasitology, Anhui Key Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, China Anhui Key Laboratory of Zoonose, Anhui Medical University, Hefei, China
MINGZHAN DU
Affiliation:
Department of Pathological Anatomy, Anhui Medical University, Hefei, China
XIANGYANG HU
Affiliation:
Department of Pathological Anatomy, Anhui Medical University, Hefei, China
QIANG WU
Affiliation:
Department of Pathological Anatomy, Anhui Medical University, Hefei, China
JILONG SHEN*
Affiliation:
Department of Microbiology and Parasitology, Anhui Key Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, China Anhui Key Laboratory of Zoonose, Anhui Medical University, Hefei, China
*
*Corresponding author: Department of Microbiology and Parasitology; Anhui Key Laboratory of Microbiology and Parasitology, AMU; Anhui Key Laboratory of Zoonoses, AMU, No. 81, Meishan Road, Hefei, Anhui, China. Tel/Fax: +86 551 5113863. E-mail: [email protected]
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Summary

Interleukin (IL)-13 and alternatively activated macrophages (AAMs) play an important role in liver granuloma and fibrosis of schistosomiasis. Paeoniflorin (PAE, C23H28O11) has been reported to have an anti-hepatic fibrosis effect in schistosomiasis; however, the mechanism has not been fully elucidated. In this study, we measured serum hyaluronic acid (HA) concentrations, liver granuloma diameter and volume density, fibrosis degree and expressions of IL-13, arginase-1 (ARG-1), nitric oxide synthase-2 (NOS-2), and phosphorylated signal transducer and activator of transcription 6 (p-STAT6) in mice liver of schistosomiasis. Then we detected expressions of specific biomarkers of AAMs and activity of Arg-1 in Kupffer cells (KCs) from infected and PAE-treated mice, or in KCs from uninfected mice, but exposed to rIL-13 in vitro. Finally, we observed expression of IL-13 signalling molecules in KCs and secretion of IL-13 from lymphocytes of infected and PAE-treated mice. Our results showed that during schistosomiasis, IL-13 expression and secretion increased with liver macrophages activated alternatively. PAE not only directly inhibited alternative activation of macrophages via reducing the phosphorylations of janus-activated kinase 2 (JAK2) and/or STAT6, leading to reduction of AAMs-related markers and Arg-1 activity, but also indirectly suppressed alternative activation of macrophages through decreasing secretion of IL-13. PAE might be a promising prophylactic agent for hepatic granuloma and fibrosis of schistosomiasis japonica.

Keywords

Schistosoma japonicumalternatively activated macrophagepaeoniflorinfibrosisinterleukin-13arginase-1
Type
Research Article
Information
Parasitology , Volume 138 , Issue 10 , September 2011 , pp. 1259 - 1271
Copyright
Copyright © Cambridge University Press 2011

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References

REFERENCES

Abdallahi, O. M., Bensalem, H., Augier, R., Diagana, M., De Reggi, M. and Gharib, B. (2001). Arginase expression in peritoneal macrophages and increase in circulating polyamine levels in mice infected with Schistosoma mansoni. Cellular and Molecular Life Sciences 58, 1350–1357.CrossRefGoogle ScholarPubMed
Aly, I. R., Hendawy, M. A., Ali, E., Hassan, E. and Nosseir, M. M. (2010). Immunological and parasitological parameters after treatment with dexamethasone in murine Schistosoma mansoni. Memórias do Instituto Oswaldo Cruz 105, 729–735. doi: S0074-02762010000600001 [pii].CrossRefGoogle ScholarPubMed
Bartley, P. B., Ramm, G. A., Jones, M. K., Ruddell, R. G., Li, Y. and McManus, D. P. (2006). A contributory role for activated hepatic stellate cells in the dynamics of Schistosoma japonicum egg-induced fibrosis. International Journal for Parasitology 36, 993–1001. doi: S0020-7519(06)00151-2 [pii]10.1016/j.ijpara.2006.04.015.CrossRefGoogle ScholarPubMed
Burke, M. L., Jones, M. K., Gobert, G. N., Li, Y. S., Ellis, M. K. and McManus, D. P. (2009). Immunopathogenesis of human schistosomiasis. Parasite Immunology 31, 163–176. doi: PIM1098 [pii]10.1111/j.1365-3024.2009.01098.x.CrossRefGoogle ScholarPubMed
Cheever, A. W., Finkelman, F. D., Caspar, P., Heiny, S., Macedonia, J. G. and Sher, A. (1992). Treatment with anti-IL-2 antibodies reduces hepatic pathology and eosinophilia in Schistosoma mansoni-infected mice while selectively inhibiting T cell IL-5 production. The Journal of Immunology 148, 3244–3248.CrossRefGoogle ScholarPubMed
Cheever, A. W., Williams, M. E., Wynn, T. A., Finkelman, F. D., Seder, R. A., Cox, T. M., Heiny, S., Caspar, P. and Sher, A. (1994). Anti-IL-4 treatment of Schistosoma mansoni-infected mice inhibits development of T cells and non-B, non-T cells expressing Th2 cytokines while decreasing egg-induced hepatic fibrosis. The Journal of Immunology 153, 753–759.CrossRefGoogle ScholarPubMed
Chiaramonte, M. G., Donaldson, D. D., Cheever, A. W. and Wynn, T. A. (1999). An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. The Journal of Clinical Investigation 104, 777–785. doi: 10.1172/JCI7325.CrossRefGoogle ScholarPubMed
Chiaramonte, M. G., James, A. W. C., Malley, D., Donaldson, D. D. and Wynn, T. A. (2001). Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis. Hepatology 34, 273–282.CrossRefGoogle ScholarPubMed
Chu, D., Li, C., Wu, Q. and Shen, J. (2008). Paeoniflorin prevents hepatic fibrosis of Schistosomiasis japonica by inhibiting TGF-β1 production from macrophages in mice. Frontiers of Medicine in China 2, 154–165. doi: 10.1007/s11684-008-0029-7.CrossRefGoogle Scholar
Chu, D. Y., Luo, Q. L., Li, C. L., Gao, Y. F., Yu, L., Wei, W., Wu, Q. and Shen, J. L. (2007). Paeoniflorin inhibits TGF-beta1-mediated collagen production by Schistosoma japonicum soluble egg antigen in vitro. Parasitology 134, 1611–1621.CrossRefGoogle ScholarPubMed
Cioli, D. and Pica-Mattoccia, L. (2003). Praziquantel. Parasitology Research 90 (Supp 1), S3–S9.CrossRefGoogle ScholarPubMed
Dewals, B. G., Marillier, R. G., Hoving, J. C., Leeto, M., Schwegmann, A. and Brombacher, F. (2010). IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. PLoS Neglected Tropical Diseases 4, e689. doi: 10.1371/journal.pntd.0000689.CrossRefGoogle ScholarPubMed
Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R. and Iredale, J. P. (2005). Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. The Journal of Clinical Investigation 115, 56–65. doi: 10.1172/JCI22675.CrossRefGoogle ScholarPubMed
Duvall, R. H. and DeWitt, W. B. (1967). An improved perfusion technique for recovering adult schistosomes from laboratory animals. American Journal of Tropical Medicine and Hygiene 16, 483–486.CrossRefGoogle ScholarPubMed
Fong, C. H., Bebien, M., Didierlaurent, A., Nebauer, R., Hussell, T., Broide, D., Karin, M. and Lawrence, T. (2008). An antiinflammatory role for IKKbeta through the inhibition of “classical” macrophage activation. The Journal of Experimental Medicine 205, 1269–1276. doi: jem.20080124 [pii]10.1084/jem.20080124.CrossRefGoogle ScholarPubMed
Gryseels, B., Polman, K., Clerinx, J. and Kestens, L. (2006). Human schistosomiasis. Lancet 368, 1106–1118.CrossRefGoogle ScholarPubMed
Hesse, M., Modolell, M., La Flamme, A. C., Schito, M., Fuentes, J. M., Cheever, A. W., Pearce, E. J. and Wynn, T. A. (2001). Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. The Journal of Immunology 167, 6533–6544.CrossRefGoogle ScholarPubMed
King, C. H. (2009). Toward the elimination of schistosomiasis. The New England Journal of Medicine 360, 106–109. doi: 360/2/106 [pii]10.1056/NEJMp0808041.CrossRefGoogle ScholarPubMed
Kononen, J., Bubendorf, L., Kallioniemi, A., Barlund, M., Schraml, P., Leighton, S., Torhorst, J., Mihatsch, M. J., Sauter, G. and Kallioniemi, O. P. (1998). Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nature Medicine 4, 844–847.CrossRefGoogle ScholarPubMed
Lappalainen, K., Jaaskelainen, I., Syrjanen, K., Urtti, A. and Syrjanen, S. (1994). Comparison of cell proliferation and toxicity assays using two cationic liposomes. Pharmaceutical Research 11, 1127–1131.CrossRefGoogle ScholarPubMed
Li, X., Shen, J., Zhong, Z., Peng, J., Wen, H., Li, J., Luo, Q. and Wei, W. (2010). Paeoniflorin ameliorates schistosomiasis liver fibrosis through regulating IL-13 and its signalling molecules in mice. Parasitology 137, 1213–1225. doi: 10.1017/s003118201000003x.CrossRefGoogle ScholarPubMed
Ouyang, J., Guzman, M., Desoto-Lapaix, F., Pincus, M. R. and Wieczorek, R. (2009). Utility of desmin and a Masson's trichrome method to detect early acute myocardial infarction in autopsy tissues. International Journal of Clinical and Experimental Pathology 3, 98–105.Google Scholar
Pearce, E. J. and MacDonald, A. S. (2002). The immunobiology of schistosomiasis. Nature Reviews Immunology 2, 499–511. doi: 10.1038/nri843nri843 [pii].CrossRefGoogle ScholarPubMed
Pesce, J. T., Ramalingam, T. R., Mentink-Kane, M. M., Wilson, M. S., El Kasmi, K. C., Smith, A. M., Thompson, R. W., Cheever, A. W., Murray, P. J. and Wynn, T. A. (2009). Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathogens 5, e1000371. doi: 10.1371/journal.ppat.1000371.CrossRefGoogle ScholarPubMed
Prasse, A., Pechkovsky, D. V., Toews, G. B., Jungraithmayr, W., Kollert, F., Goldmann, T., Vollmer, E., Muller-Quernheim, J. and Zissel, G. (2006). A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18. American Journal of Respiratory and Critical Care Medicine 173, 781–792. doi: 200509-1518OC [pii]10.1164/rccm.200509-1518OC.CrossRefGoogle ScholarPubMed
Reiman, R. M., Thompson, R. W., Feng, C. G., Hari, D., Knight, R., Cheever, A. W., Rosenberg, H. F. and Wynn, T. A. (2006). Interleukin-5 (IL-5) augments the progression of liver fibrosis by regulating IL-13 activity. Infection and Immunity 74, 1471–1479. doi: 74/3/1471 [pii]10.1128/IAI.74.3.1471-1479.2006.CrossRefGoogle ScholarPubMed
Reyes, J. L. and Terrazas, L. I. (2007). The divergent roles of alternatively activated macrophages in helminthic infections. Parasite Immunology 29, 609–619. doi: PIM973 [pii]10.1111/j.1365-3024.2007.00973.x.CrossRefGoogle ScholarPubMed
Ross, A. G., Bartley, P. B., Sleigh, A. C., Olds, G. R., Li, Y., Williams, G. M. and McManus, D. P. (2002). Schistosomiasis. The New England Journal of Medicine 346, 1212–1220. doi: 10.1056/NEJMra012396346/16/1212 [pii].CrossRefGoogle ScholarPubMed
Roy, B., Bhattacharjee, A., Xu, B., Ford, D., Maizel, A. L. and Cathcart, M. K. (2002). IL-13 signal transduction in human monocytes: phosphorylation of receptor components, association with Jaks, and phosphorylation/activation of Stats. Journal of Leukocyte Biology 72, 580–589.CrossRefGoogle ScholarPubMed
Shearer, J. D., Richards, J. R., Mills, C. D. and Caldwell, M. D. (1997). Differential regulation of macrophage arginine metabolism: a proposed role in wound healing. American Journal of Physiology 272, E181–E190.Google ScholarPubMed
Southgate, V. R., Rollinson, D., Tchuem Tchuente, L. A. and Hagan, P. (2005). Towards control of schistosomiasis in sub-Saharan Africa. Journal of Helminthology 79, 181–185.CrossRefGoogle ScholarPubMed
Stickings, P., Mistry, S. K., Boucher, J. L., Morris, S. M. and Cunningham, J. M. (2002). Arginase expression and modulation of IL-1beta-induced nitric oxide generation in rat and human islets of Langerhans. Nitric Oxide 7, 289–296. doi: S1089860302001222 [pii].CrossRefGoogle ScholarPubMed
Stolfi, C., Caruso, R., Franze, E., Sarra, M., De Nitto, D., Rizzo, A., Pallone, F. and Monteleone, G. (2010). Interleukin-25 fails to activate STAT6 and induce alternatively activated macrophages. Immunology 132, 66–77. doi: 10.1111/j.1365-2567.2010.03340.xCrossRefGoogle ScholarPubMed
Tsuboi, H., Hossain, K., Akhand, A. A., Takeda, K., Du, J., Rifa'i, M., Dai, Y., Hayakawa, A., Suzuki, H. and Nakashima, I. (2004). Paeoniflorin induces apoptosis of lymphocytes through a redox-linked mechanism. Journal of Cellular Biochemistry 93, 162–172.CrossRefGoogle ScholarPubMed
Wilson, M. S., Mentink-Kane, M. M., Pesce, J. T., Ramalingam, T. R., Thompson, R. and Wynn, T. A. (2007). Immunopathology of schistosomiasis. Immunology and Cell Biology 85, 148–154. doi: 7100014 [pii]10.1038/sj.icb.7100014.CrossRefGoogle ScholarPubMed
Wu, J. B., Chuang, H. R., Yang, L. C. and Lin, W. C. (2010). A standardized aqueous extract of Anoectochilus formosanus ameliorated thioacetamide-induced liver fibrosis in mice: the role of Kupffer cells. Bioscience, Biotechnology, and Biochemistry 74, 781–787. doi: JST.JSTAGE/bbb/90824 [pii].CrossRefGoogle ScholarPubMed
Wynn, T. A. and Barron, L. (2010). Macrophages: master regulators of inflammation and fibrosis. Seminars in Liver Disease 30, 245–257. doi: 10.1055/s-0030-1255354.CrossRefGoogle ScholarPubMed
Wynn, T. A., Thompson, R. W., Cheever, A. W. and Mentink-Kane, M. M. (2004). Immunopathogenesis of schistosomiasis. Immunological Reviews 201, 156–167. doi: 10.1111/j.0105-2896.2004.00176.xIMR176 [pii].CrossRefGoogle ScholarPubMed
Xuan, Y. T., Guo, Y., Han, H., Zhu, Y. and Bolli, R. (2001). An essential role of the JAK-STAT pathway in ischemic preconditioning. Proceedings of the National Academy of Sciences, USA 98, 9050–9055. doi: 10.1073/pnas.16128379898/16/9050 [pii].CrossRefGoogle ScholarPubMed
Yamahara, J., Yamada, T., Kimura, H., Sawada, T. and Fujimura, H. (1982). Biologically active principles of crude drugs: Antiallergic principles of “shoseiryu-to”:l.Effect on delayed-type allergy reaction. Yakugaku Zasshi 102, 881–886.CrossRefGoogle Scholar
Zhang, J. P., Zhang, M., Jin, C., Zhou, B., Xie, W. F., Guo, C., Zhang, C. and Qian, D. H. (2001). Matrine inhibits production and actions of fibrogenic cytokines released by mouse peritoneal macrophages. Acta Pharmacologica Sinica 22, 765–768.Google ScholarPubMed
Zhang, L. L., Wei, W., Wang, N. P., Wang, Q. T., Chen, J. Y., Chen, Y., Wu, H. and Hu, X. Y. (2008). Paeoniflorin suppresses inflammatory mediator production and regulates G protein-coupled signaling in fibroblast-like synoviocytes of collagen induced arthritic rats. Inflammation Research 57, 388–395. doi: 10.1007/s00011-007-7240-x.CrossRefGoogle ScholarPubMed