Hostname: page-component-848d4c4894-sjtt6 Total loading time: 0 Render date: 2024-06-24T20:58:20.144Z Has data issue: false hasContentIssue false
  • English
  • Français

Paeoniflorin ameliorates schistosomiasis liver fibrosis through regulating IL-13 and its signalling molecules in mice

Published online by Cambridge University Press:  19 April 2010

XIAOYUE LI ,
JILONG SHEN ,
ZHENGRONG ZHONG ,
JUN PENG ,
HUIQIN WEN ,
JING LI ,
QINGLI LUO  and
WEI WEI
XIAOYUE LI
Affiliation:
Institute of Clinical Pharmacology, Anhui Medical University Provincial Laboratory of Zoonoses, Anhui Medical University Key Laboratory of Microbiology and Parasitology Anhui, Anhui Medical University Key Laboratory of Gene Resource Utilization for Severe Diseases, Ministry of Education of China, Hefei, P R China
JILONG SHEN*
Affiliation:
Institute of Clinical Pharmacology, Anhui Medical University Provincial Laboratory of Zoonoses, Anhui Medical University Key Laboratory of Microbiology and Parasitology Anhui, Anhui Medical University Key Laboratory of Gene Resource Utilization for Severe Diseases, Ministry of Education of China, Hefei, P R China
ZHENGRONG ZHONG
Affiliation:
Institute of Clinical Pharmacology, Anhui Medical University Provincial Laboratory of Zoonoses, Anhui Medical University Key Laboratory of Microbiology and Parasitology Anhui, Anhui Medical University Key Laboratory of Gene Resource Utilization for Severe Diseases, Ministry of Education of China, Hefei, P R China
JUN PENG
Affiliation:
Department of Pathology, Anhui Medical University Hospital of An Qing, P R China
HUIQIN WEN
Affiliation:
Provincial Laboratory of Zoonoses, Anhui Medical University Key Laboratory of Microbiology and Parasitology Anhui, Anhui Medical University Key Laboratory of Gene Resource Utilization for Severe Diseases, Ministry of Education of China, Hefei, P R China
JING LI
Affiliation:
Provincial Laboratory of Zoonoses, Anhui Medical University Key Laboratory of Microbiology and Parasitology Anhui, Anhui Medical University Key Laboratory of Gene Resource Utilization for Severe Diseases, Ministry of Education of China, Hefei, P R China
QINGLI LUO
Affiliation:
Provincial Laboratory of Zoonoses, Anhui Medical University Key Laboratory of Microbiology and Parasitology Anhui, Anhui Medical University Key Laboratory of Gene Resource Utilization for Severe Diseases, Ministry of Education of China, Hefei, P R China
WEI WEI
Affiliation:
Institute of Clinical Pharmacology, Anhui Medical University
*
*Corresponding author: Provincial Laboratory of Zoonoses, Anhui Medical University, No. 81, Meishan Road, Hefei, China. Tel/Fax: +86 551 5113863. E-mail: shenjilong53@126.com
Get access Rights & Permissions [Opens in a new window]

Summary

Treatment of liver fibrosis associated with Schistosoma japonicum ova-induced granulomas remains a challenging proposition. Paeoniflorin (PAE, C23H28O11) has anti-inflammatory, anti-allergic, and immunoregulatory effects and it is commonly used in Chinese Herbal prescriptions to treat hepatic disorders. The present study was carried out to investigate the effects of PAE on hepatic fibrosis of mice infected with S. japonicum and to explore its possible mechanism. Upon pathological examination of PAE-treated mice, the size of egg granuloma, fibrosis scores, the concentration of IL-13 and hydroxyproline in liver were significantly reduced compared with the model mice. In the primary culture of hepatic stellate cells (HSCs), PAE inhibited IL-13-induced collagen synthesis. These results suggested that PAE might alleviate the hepatic granulomas and fibrosis caused by S. japonicum and the inhibitory effect of PAE on hepatic fibrosis might be associated with its ability to decrease the level of IL-13 and to interfere with the IL-13 signalling molecule in HSCs.

Keywords

paeoniflorinschistosomiasisliver fibrosishepatic stellate cellIL-13suppressor of cytokine signalling-1STAT6
Type
Research Article
Information
Parasitology , Volume 137 , Issue 8 , July 2010 , pp. 1213 - 1225
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alves Oliveira, L. F., Moreno, E. C., Gazzinelli, G., Martins-Filho, O. A., Silveira, A. M., Gazzinelli, A., Malaquias, L. C., Loverde, P., Leite, P. M. and Correa-Oliveira, R. (2006). Cytokine production associated with periportal fibrosis during chronic schistosomiasis mansoni in humans. Infection and Immunity 74, 1215–1221.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.CrossRefGoogle ScholarPubMed
Chan, K., Liu, Z. Q., Jiang, Z. H., Zhou, H., Wong, Y. F., Xu, H. X. and Liu, L. (2006). The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model. Journal of Ethnopharmacology 103, 425–432.CrossRefGoogle ScholarPubMed
Chang, D., Ramalho, L. N., Ramalho, F. S., Martinelli, A. L. and Zucoloto, S. (2006). Hepatic stellate cells in human schistosomiasis mansoni: a comparative immunohistochemical study with liver cirrhosis. Acta Tropica 97, 318–323.CrossRefGoogle ScholarPubMed
Chen, F., Cai, W., Chen, Z., Chen, X. and Liu, R. (2002). Dynamic changes in the collagen metabolism of liver fibrosis at the transcription level in rabbits with Schistosomiasis japonica. Chinese Medicine Journal (English) 115, 1637–1640.Google ScholarPubMed
Chiaramonte, M. G., Cheever, A. W., Malley, J. 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
Chiaramonte, M. G., Donaldson, D. D., Cheever, A. W. and Wynn, T. A. (1999 a). An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. Journal of Clinical Investigation, 104, 777–785.CrossRefGoogle ScholarPubMed
Chiaramonte, M. G., Mentink-Kane, M., Jacobson, B. A., Cheever, A. W., Whitters, M. J., Goad, M. E., Wong, A., Collins, M., Donaldson, D. D., Grusby, M. J. and Wynn, T. A. (2003). Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response. Journal of Experimental Medicine 197, 687–701.CrossRefGoogle Scholar
Chiaramonte, M. G., Schopf, L. R., Neben, T. Y., Cheever, A. W., Donaldson, D. D. and Wynn, T. A. (1999 b). IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs. Journal of Immunology 162, 920–930.CrossRefGoogle ScholarPubMed
Chu, D., Luo, Q., Li, C., Gao, Y., Yu, L., Wei, W., Wu, Q. and Shen, J. (2007). Paeoniflorin inhibits TGF-beta1-mediated collagen production by Schistosoma japonicum soluble egg antigen in vitro. Parasitology 134, 1611–1621.CrossRefGoogle ScholarPubMed
Chu, D. Y., Li, C. L., Yang, F., Wu, Q., Li, J., Ding, X. D., Luo, Q. L. and Shen, J. L. (2008). [Effect of paeoniflorin on hepatic immunopathogenesis in mice with Schistosoma japonicum infection]. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 26, 10–15, 20.Google ScholarPubMed
Coutinho, H. M., Acosta, L. P., Wu, H. W., Mcgarvey, S. T., Su, L., Langdon, G. C., Jiz, M. A., Jarilla, B., Olveda, R. M., Friedman, J. F. and Kurtis, J. D. (2007). Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection. Journal of Infectious Diseases 195, 288–295.CrossRefGoogle ScholarPubMed
De Jesus, A. R., Magalhaes, A., Miranda, D. G., Miranda, R. G., Araujo, M. I., De Jesus, A. A., Silva, A., Santana, L. B., Pearce, E. and Carvalho, E. M. (2004). Association of type 2 cytokines with hepatic fibrosis in human Schistosoma mansoni infection. Infection and Immunity 72, 3391–3397.CrossRefGoogle ScholarPubMed
Dickensheets, H. L., Venkataraman, C., Schindler, U. and Donnelly, R. P. (1999). Interferons inhibit activation of STAT6 by interleukin 4 in human monocytes by inducing SOCS-1 gene expression. Proceedings of the National Academy of Sciences, USA 96, 10800–10805.CrossRefGoogle ScholarPubMed
Ga., R. (1998). Isolation and culture of rat hepatic stellate cells. Journal of Gastroenterology and Hepatology 13, 846–851.Google Scholar
Granel, B., Chevillard, C. and Dessein, A. (2007). [Interleukin 13 and interleukin 13 receptor involvement in systemic sclerosis]. Revue de Medicne Interne 28, 613–622.CrossRefGoogle ScholarPubMed
Greenwald, B. (2005). Schistosomiasis: implications for world travelers and healthcare providers. Gastroenterology Nursing 28, 203–205; quiz 206–207.CrossRefGoogle ScholarPubMed
Gressner, A. M. (1998). The cell biology of liver fibrogenesis – an imbalance of proliferation, growth arrest and apoptosis of myofibroblasts. Cell and Tissue Research 292, 447–452.CrossRefGoogle ScholarPubMed
Gui, S. Y., Wei, W., Wang, H., Wu, L., Sun, W. Y., Chen, W. B. and Wu, C. Y. (2006). Effects and mechanisms of crude astragalosides fraction on liver fibrosis in rats. Journal of Ethnopharmacology 103, 154–159.CrossRefGoogle ScholarPubMed
Hebenstreit, D., Luft, P., Schmiedlechner, A., Regl, G., Frischauf, A. M., Aberger, F., Duschl, A. and Horejs-Hoeck, J. (2003). IL-4 and IL-13 induce SOCS-1 gene expression in A549 cells by three functional STAT6-binding motifs located upstream of the transcription initiation site. Journal of Immunology 171, 5901–5907.CrossRefGoogle ScholarPubMed
Hershey, G. K. (2003). IL-13 receptors and signaling pathways: an evolving web. Journal of Allergy and Clinical Immunology 111, 677–690; quiz 691.CrossRefGoogle ScholarPubMed
Hiroyasu Shoda, A. Y., Ryouhei Nishino, , Taku Nakashima, , Nobuhisa Ishikawa, Y. H., Noboru Hattori, and Tetsuji Naka, N. K. (2007). Overproduction of collagen and diminished SOCS1 expression are causally linked in fibroblasts from idiopathic pulmonary fibrosis. Biochemical and Biophysical Research Communications 353, 1004–1010.CrossRefGoogle Scholar
Hsu, Y. C., Chiu, Y. T., Cheng, C. C., Wu, C. F., Lin, Y. L. and Huang, Y. T. (2007). Antifibrotic effects of tetrandrine on hepatic stellate cells and rats with liver fibrosis. Journal of Gastroenterology and Hepatology 22, 99–111.CrossRefGoogle ScholarPubMed
Huang, H., Chang, E. J., Lee, Y., Kim, J. S., Kang, S. S. and Kim, H. H. (2008). A genome-wide microarray analysis reveals anti-inflammatory target genes of paeonol in macrophages. Inflammation Research 57, 189–198.CrossRefGoogle ScholarPubMed
Hung, J. Y., Yang, C. J., Tsai, Y. M., Huang, H. W. and Huang, M. S. (2008). Antiproliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligand-mediated apoptotic pathway in human non-small cell lung cancer A549 cells. Clinical and Experimental Pharmacology and Physiology 35, 141–147.CrossRefGoogle ScholarPubMed
Jinnin, M., Ihn, H., Yamane, K. and Tamaki, K. (2004). Interleukin-13 stimulates the transcription of the human alpha2(I) collagen gene in human dermal fibroblasts. Journal of Biological Chemistry 279, 41783–41791.CrossRefGoogle ScholarPubMed
Kaplan, M. H., Whitfield, J. R., Boros, D. L. and Grusby, M. J. (1998). Th2 cells are required for the Schistosoma mansoni egg-induced granulomatous response. Journal of Immunology 160, 1850–1856.CrossRefGoogle ScholarPubMed
Kelly-Welch, A., Hanson, E. M. and Keegan, A. D. (2005). Interleukin-13 (IL-13) pathway. Science's STKE:Signal Transduction Knowledge Environment 293, cm8.Google Scholar
Kimura, M., Kimura, I. and Nojima, H. (1985). Depolarizing neuromuscular blocking action induced by electropharmacological coupling in the combined effect of paeoniflorin and glycyrrhizin. Japanese Journal of Pharmacology 37, 395–399.CrossRefGoogle ScholarPubMed
Kimura, M., Kimura, I., Takahashi, K., Muroi, M., Yoshizaki, M., Kanaoka, M. and Kitagawa, I. (1984). Blocking effects of blended paeoniflorin or its related compounds with glycyrrhizin on neuromuscular junctions in frog and mouse. Japanese Journal of Pharmacology 36, 275–282.CrossRefGoogle ScholarPubMed
Lee, B., Shin, Y. W., Bae, E. A., Han, S. J., Kim, J. S., Kang, S. S. and Kim, D. H. (2008). Antiallergic effect of the root of Paeonia lactiflora and its constituents paeoniflorin and paeonol. Archives of Pharmacology Research 31, 445–450.CrossRefGoogle ScholarPubMed
Li, C., Luo, J., Li, L., Cheng, M., Huang, N., Liu, J. and Waalkes, M. P. (2003). The collagenolytic effects of the traditional Chinese medicine preparation, Han-Dan-Gan-Le, contribute to reversal of chemical-induced liver fibrosis in rats. Life Science 72, 1563–1571.CrossRefGoogle ScholarPubMed
Liu, D. F., Wei, W. and Song, L. H. (2006). Protective effect of paeoniflorin on immunological liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide: modulation of tumour necrosis factor-alpha and interleukin-6 MRNA. Clinical and Experimental Pharmacology and Physiology 33, 332–339.CrossRefGoogle ScholarPubMed
Magalhaes, A., Miranda, D. G., Miranda, R. G., Araujo, M. I., Jesus, A. A., Silva, A., Santana, L. B., Pearce, E., Carvalho, E. M. and Jesus, A. R. (2004). Cytokine profile associated with human chronic Schistosomiasis mansoni. Memórias do Instituto Oswaldo Cruz 99, 21–26.CrossRefGoogle ScholarPubMed
Mckenzie, G. J., Bancroft, A., Grencis, R. K. and Mckenzie, A. N. (1998). A distinct role for interleukin-13 in Th2-cell-mediated immune responses. Current Biology 8, 339–342.CrossRefGoogle ScholarPubMed
Mckenzie, A. N., Culpepper, J. A., De Waal Malefyt, R., Briere, F., Punnonen, J., Aversa, G., Sato, A., Dang, W., Cocks, B. G., Menon, S., De Vries, J. E., Banchereau, J. and Zurawski, G. (1993). Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proceedings of the National Academy of Sciences, USA 90, 3735–3739.CrossRefGoogle ScholarPubMed
Mckenzie, A. N. and Fallon, P. G. (2003). Decoy receptors in the regulation of T helper cell type 2 responses. Journal of Experimental Medicine 197, 675–679.CrossRefGoogle ScholarPubMed
Minty, A., Chalon, P., Derocq, J. M., Dumont, X., Guillemot, J. C., Kaghad, M., Labit, C., Leplatois, P., Liauzun, P., Miloux, B., Minty, C., Casellas, P., Loison, G., Lupker, J., Shire, D., Ferrara, P. and Caput, D. (1993). Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature, London 362, 248–250.CrossRefGoogle ScholarPubMed
Nakashima, T., Yokoyama, A., Onari, Y., Shoda, H., Haruta, Y., Hattori, N., Naka, T. and Kohno, N. (2008). Suppressor of cytokine signaling 1 inhibits pulmonary inflammation and fibrosis. Journal of Allergy and Clinical Immunology 121, 1269–1276.CrossRefGoogle ScholarPubMed
Smith, P. F. (2008). Inflammation in Parkinson's disease: an update. Current Opinion in Investigational Drugs 9, 478–484.Google ScholarPubMed
Sugimoto, R., Enjoji, M., Nakamuta, M., Ohta, S., Kohjima, M., Fukushima, M., Kuniyoshi, M., Arimura, E., Morizono, S., Kotoh, K. and Nawata, H. (2005). Effect of IL-4 and IL-13 on collagen production in cultured LI90 human hepatic stellate cells. Liver International 25, 420–428.CrossRefGoogle ScholarPubMed
Sun, W. Y., Wei, W., Wu, L., Gui, S. Y. and Wang, H. (2007). Effects and mechanisms of extract from Paeonia lactiflora and Astragalus membranaceus on liver fibrosis induced by carbon tetrachloride in rats. Journal of Ethnopharmacology 112, 514–523.CrossRefGoogle ScholarPubMed
Ta, W. (2008). Cellular and molecular mechanisms of fibrosis. Journal of Pathology 214, 199–210.Google Scholar
Takagi, K. and Harada, M. (1969). [Pharmacological studies on herb paeony root. II. Anti-inflammatory effect, inhibitory effect on gastric juice secretion, preventive effect on stress ulcer, antidiuretic effect of paeoniflorin and combined effects with licorice component Fm 100]. Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan 89, 887–892.CrossRefGoogle ScholarPubMed
Takayama, G., Arima, K., Kanaji, T., Toda, S., Tanaka, H., Shoji, S., Mckenzie, A. N., Nagai, H., Hotokebuchi, T. and Izuhara, K. (2006). Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. Journal of Allergy and Clinical Immunology 118, 98–104.CrossRefGoogle ScholarPubMed
Talaat, R. M., El-Bassiouny, A. I., Osman, A. M., Yossif, M., Charmy, R. and Al-Sherbiny, M. M. (2007). Cytokine secretion profile associated with periportal fibrosis in S. mansoni-infected Egyptian patients. Parasitology Research 101, 289–299.CrossRefGoogle Scholar
Tsukada, S., Parsons, C. J. and Rippe, R. A. (2006). Mechanisms of liver fibrosis. Clinica Chimica Acta 364, 33–60.CrossRefGoogle ScholarPubMed
Wang, H., Wei, W., Wang, N. P., Wu, C. Y., Yan, S. X., Yue, L., Zhang, L. L. and Xu, S. Y. (2005). Effects of total glucosides of peony on immunological hepatic fibrosis in rats. World Journal of Gastroenterology 11, 2124–2129.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.CrossRefGoogle ScholarPubMed
Wong, W. S. and Leong, K. P. (2004). Tyrosine kinase inhibitors: a new approach for asthma. Biochimica et Biophysica Acta 1697, 53–69.CrossRefGoogle ScholarPubMed
Wu, H., Wei, W., Song, L., Zhang, L., Chen, Y. and Hu, X. (2007). Paeoniflorin induced immune tolerance of mesenteric lymph node lymphocytes via enhancing beta 2-adrenergic receptor desensitization in rats with adjuvant arthritis. International Immunopharmacology 7, 662–673.CrossRefGoogle ScholarPubMed
Wynn, T. A. (2003). IL-13 effector functions. Annual Review of Immunology 21, 425–456.CrossRefGoogle ScholarPubMed
Wynn, T. A., Hesse, M., Sandler, N. G., Kaviratne, M., Hoffmann, K. F., Chiaramonte, M. G., Reiman, R., Cheever, A. W., Sypek, J. P. and Mentink-Kane, M. M. (2004). P-selectin suppresses hepatic inflammation and fibrosis in mice by regulating interferon gamma and the IL-13 decoy receptor. Hepatology 39, 676–687.CrossRefGoogle ScholarPubMed
Yata, Y. E. S., Suzuki, S., Li, X. K., Tamura, A., Kimura, H., Takahara, T. and Watanabe, A. (1999). An improved method for the purification of stellate cells from rat liver with dichloromethylene diphosphate (CL2MDP). Methods in Cell Science 21, 19–24.CrossRefGoogle ScholarPubMed
Yoshida, T., Ogata, H., Kamio, M., Joo, A., Shiraishi, H., Tokunaga, Y., Sata, M., Nagai, H. and Yoshimura, A. (2004). SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. Journal of Experimental Medicine 199, 1701–1707.CrossRefGoogle ScholarPubMed
Yoshimura, A. N. T. and Kubo, M. (2007). SOCS proteins, cytokine signalling and immune regulation. Nature Reviews Immunology 7, 454–465.CrossRefGoogle ScholarPubMed
Zhang, L. L., Wei, W., Wang, N. P., Wang, Q. T., Chen, J. Y., Chen, Y., Wu, H. and Hu, X. Y. (2008 a). 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.CrossRefGoogle ScholarPubMed
Zhang, X. J., Li, Z., Leung, W. M., Liu, L., Xu, H. X. and Bian, Z. X. (2008 b). The analgesic effect of paeoniflorin on neonatal maternal separation-induced visceral hyperalgesia in rats. Journal of Pain 9, 497–505.CrossRefGoogle ScholarPubMed
Zhi-Xin Zhao, Q.-X. C., Xiao-Mou Peng, , Yu-Tian Chong, , Zhi-Liang Gao, (2008). Expression of SOCS-1 in the liver tissues of chronic hepatitis B and its clinical significance. World Journal of Gastroenterology 14, 607–611.CrossRefGoogle Scholar