Hostname: page-component-586b7cd67f-t8hqh Total loading time: 0 Render date: 2024-11-27T20:56:22.331Z Has data issue: false hasContentIssue false
  • English
  • Français

Mechanism of dexamethasone in the context of Toxoplasma gondii infection

Published online by Cambridge University Press:  27 June 2017

JING ZHANG ,
XIN QIN ,
YU ZHU ,
SHUANG ZHANG ,
XUE-WEI ZHANG  and
HE LU
JING ZHANG
Affiliation:
Department of Pathogen Biology, Chongqing Medical University, Chongqing 400016, People's Republic of China Molecular Medicine and Tumor Research Center, Chongqing Medical University, Chongqing 400016, People's Republic of China
XIN QIN
Affiliation:
Department of Pathogen Biology, Chongqing Medical University, Chongqing 400016, People's Republic of China Molecular Medicine and Tumor Research Center, Chongqing Medical University, Chongqing 400016, People's Republic of China
YU ZHU
Affiliation:
Department of Pathogen Biology, Chongqing Medical University, Chongqing 400016, People's Republic of China Molecular Medicine and Tumor Research Center, Chongqing Medical University, Chongqing 400016, People's Republic of China
SHUANG ZHANG
Affiliation:
Department of Pathogen Biology, Chongqing Medical University, Chongqing 400016, People's Republic of China Molecular Medicine and Tumor Research Center, Chongqing Medical University, Chongqing 400016, People's Republic of China
XUE-WEI ZHANG
Affiliation:
Department of Pathogen Biology, Chongqing Medical University, Chongqing 400016, People's Republic of China Molecular Medicine and Tumor Research Center, Chongqing Medical University, Chongqing 400016, People's Republic of China
HE LU*
Affiliation:
Department of Pathogen Biology, Chongqing Medical University, Chongqing 400016, People's Republic of China Molecular Medicine and Tumor Research Center, Chongqing Medical University, Chongqing 400016, People's Republic of China
*
*Corresponding author. Department of Pathogen Biology, Chongqing Medical University, Chongqing 400016, People's Republic of China. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Toxoplasmosis is a serious zoonoses disease and opportunistic, and can be life-threatening. Dexamethasone (DEX) is widely used in the clinic for treatment of inflammatory and autoimmune diseases. However, long-term use of DEX is often easy to lead to acute toxoplasmosis in patients, and the potential molecular mechanism is still not very clear. The aims of this study were to investigate the effect of DEX on proliferation of Toxoplasma and its molecular mechanisms, and to establish the corresponding control measures. All the results showed that dexamethasone could enhance the proliferation of Toxoplasma gondii tachyzoites. After 72 h of DEX treatment, 566 (±7) tachyzoites were found in 100 host cells, while only 86 (±8) tachyzoites were counted from the non-treated control cells (P < 0·01). Gas chromatography (GC) analysis showed changes in level and composition of fatty acids in DEX-treated host cells, and T. gondii. Fish oil was added as a modulator of lipid metabolism in experimental mice. It was found that mice fed with fish oil did not develop the disease after infection with T. gondii, and the structure of fatty acids in plasma changed significantly. The metabolism of fatty acid in the parasites was limited, and the desaturase gene expression was downregulated. These results indicate that the molecular mechanism of dexamethasone to promote the proliferation of T. gondii may be that dexamethasone induces the change of fatty acids composition of tachyzoites and host cells. Therefore, we recommend supplementation of fatty acid in immunosuppressive and immunocompromised patients in order to inhibit toxoplasmosis.

Keywords

Toxoplasma gondiidexamethasoneproliferationfatty acid
Type
Research Article
Information
Parasitology , Volume 144 , Issue 11 , September 2017 , pp. 1551 - 1559
Check for updates
Copyright
Copyright © Cambridge University Press 2017 

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

Arlia, C. A., Svistkova, V., Mohtashami, S. and Titorenko, V. I. (2016). A novel approach to the discovery of anti-tumor pharmaceuticals: searching for activators of liponecrosis. Oncotarget 7, 5204–5225.CrossRefGoogle Scholar
Baker, C. and Antonovics, J. (2012). Evolutionary determinants of genetic variation insusceptibility to infectious diseases in humans. PLoS ONE 7, e29089.CrossRefGoogle Scholar
Boumpas, D. T., Chrousos, G. P., Wilder, R. L., Cupps, T. R. and Balow, J. E. (1993). Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Annals of Internal Medicine 119, 1198–1208.CrossRefGoogle ScholarPubMed
Brindle, R., Holliman, R., Gilks, C.and Waiyaki, P. (1991). Toxoplasma antibodies in HIV-positive patients from Nairobi. Transactions of the Royal Society of Tropical Medicine and Hygiene 85, 750–751.CrossRefGoogle ScholarPubMed
Chandrasekar, P. H. and Momin, F. (1997). Disseminated toxoplasmosis in marrow recipients, a report of three cases and a review of the literature. Bone Marrow Transplant 19, 685–689.CrossRefGoogle Scholar
Cheng, Q., Morand, E. and Yang, Y. H. (2014). Development of novel treatment strategies for inflammatory diseases-similarities and divergence between glucocorticoids and GILZ. Frontiers in Pharmacology 5, 169.CrossRefGoogle ScholarPubMed
Chomczynski, P. and Sacchi, N. (1987). Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chlorOlform extraction. Analytical Biochemistry 162, 156–159.CrossRefGoogle Scholar
Coppens, I. (2013). Targeting lipid biosynthesis and salvage in apicomplexan parasites for improved chemotherapies. Nature Reviews Microbiology 11, 823–835.CrossRefGoogle ScholarPubMed
Corporeau, C., Foll, C. L., Taouis, M., Gouygou, J. P., Bergé, J. P. and Delarue, J. (2006). Adipose tissue compensates for defect of phosphatidylinositol 3′-kinase induced in liver and muscle by dietary fish oil in fed rats. American Journal of Physiology-endocrinology and Metabolism 290, E78–E86.CrossRefGoogle ScholarPubMed
Ferreira, M. R., Chicco, A. and Lombardo, Y. B. (2013). Dietary fish oil normalized glucose-stimulated insulin secretion in isolated pancreatic islets of dyslipemic rats through mechanisms involving glucose phosphorylation, peroxisome proliferator-activated receptor and uncoupling protein 2. Prostaglandins Leukotrienes and Essential Fatty Acids 89, 31–38.CrossRefGoogle ScholarPubMed
Flaster, H., Bernhagen, J., Calandra, T. and Bucala, R. (2007). The macrophage migration inhibitory factor-glucocorticoid dyad: regulation of inflammation and immunity. Molecular Endocrinology 21, 1267–1280.CrossRefGoogle ScholarPubMed
Formaglio, P., Tavares, J., Ménard, R. and Amino, R. (2014). Loss of host cell plasma membrane integrity following cell traversal by Plasmodium sporozoites in the skin. Parasitology International 63, 237–244.CrossRefGoogle ScholarPubMed
Marra, C. A., Alaniz, M. J. D. and Brenner, R. R. (1988). A dexamethasone-induced protein stimulates D9-desaturase activity in rat liver microsomes. Biochimica Et Biophysica Acta 958, 93–98.CrossRefGoogle Scholar
Morhun, P. J., Weisz, J. M., Elias, S. J. and Holland, G. N. (1996). Recurrent ocular toxoplasmosis in patients treated with systemic corticosteroids. Retina 16, 383–387.CrossRefGoogle ScholarPubMed
Mulvihill, M. M. and Nomura, D. K. (2013). Therapeutic potential of monoacylglycerol lipase inhibitors. Life Sciences 92, 492–497.CrossRefGoogle ScholarPubMed
Parmley, S., Slifer, T. and Araujo, F. (2002). Protective effects of immunization with a recombinant cyst antigen in mouse models of infection with Toxoplasma gondii tissue cysts. Journal of Infectious Diseases 185, 2607–2610.CrossRefGoogle ScholarPubMed
Ramakrishnan, S., Docampo, M. D., Macrae, J. I., Pujol, F. M., Brooks, C. F., van Dooren, G. G., Hiltunen, J. K., Kastaniotis, A. J., McConville, M. J. and Striepen, B. (2012). Apicoplast and endoplasmic reticulum cooperate in fatty acid biosynthesis in apicomplexan parasite Toxoplasma gondii . Journal of Biological Chemistry 287, 4957–4971.CrossRefGoogle ScholarPubMed
Ramakrishnan, S., Serricchio, M., Striepen, B. and Bütikofer, P. (2013). Lipid synthesis in protozoan parasites: a comparison between kinetoplastids and apicomplexans. Progress in Lipid Research 52, 488–512.CrossRefGoogle ScholarPubMed
Ramakrishnan, S., Docampo, M. D., MacRae, J. I., Ralton, J. E., Rupasinghe, T., McConville, M. J. and Striepen, B. (2015). The intracellular parasite Toxoplasma gondii depends on the synthesis of long-chain and very long-chain unsaturated fatty acids not supplied by the host cell. Molecular Microbiology 97, 64–76.CrossRefGoogle Scholar
Rhen, T. and Cidlowski, J. A. (2005). Antiinflammatory action of glucocorticoids–new mechanisms for old drugs. New England Journal of Medicine 353, 1711–1723.CrossRefGoogle ScholarPubMed
Roberts, C. W., McLeod, R., Rice, D. W., Ginger, M., Chance, M. L. and Goad, L. J. (2003). Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa. Molecular and Biochemical Parasitology 126, 129–142.CrossRefGoogle ScholarPubMed
Schmid, W., Cole, T. J., Blendy, J. A. and Schutz, G. (1995). Molecular genetic analysis of glucocorticoid signalling in development. Journal of Steroid Biochemistry and Molecular Biology 53, 33–35.CrossRefGoogle ScholarPubMed
Shamseddin, J., Akhlaghi, L., Razmjou, E., Shojaee, S., Monavari, S. H., Tajik, N., Ebrahimi, S. A. and Meamar, A. R. (2015). Conjugated linoleic acid stimulates apoptosis in RH and tehran strains of Toxoplasma gondii, in vitro . Iranian Journal of Parasitology 10, 238–244.Google ScholarPubMed
Suutari, M., Linkkonen, K. and Laakso, S. (1990). Temperature adaptation in yeast: the role of fatty acids. Journal of General Microbiology 136, 1469–1474.CrossRefGoogle ScholarPubMed
Vandevyver, S., Dejager, L., Tuckermann, J. and Libert, C. (2013). New insights into the anti-inflammatory mechanisms of glucocorticoids: an emerging role for glucocorticoid-receptor-mediated transactivation. Endocrinology 154, 993–1007.CrossRefGoogle ScholarPubMed
Vrinten, P., Wu, G., Truksa, M. and Qiu, X. (2007). Production of polyunsaturated fatty acids in transgenic plants. Biotechnol Genet Eng Rev 24, 263–279.CrossRefGoogle ScholarPubMed
Wang, T., Li, J. F., Wang, W. Y., Li, X., Zhou, X. O. and Zhao, Z. J. (2014). Effect of dexamethasone on the anti Toxoplasma effect of peritoneal macrophages in rats. Chinese Journal of Pathogen Biology 2, 101–104.Google Scholar
Welti, R., Mui, E., Sparks, A., Wernimont, S., Isaac, G., Kirisits, M., Roth, M., Roberts, C. W., Botté, C., Maréchal, E. and McLeod, R. (2007). Lipidomic analysis of Toxoplasma gondii reveals unusual polarlipids. Biochemistry 46, 13882–13890.CrossRefGoogle Scholar
Wu, Y., Zhao, W., Zhao, J., Qin, W., Pan, J., Bauman, W. A., Blitzer, R. D. and Cardozo, C. (2010). REDD1 is a major target of testosterone action in preventing dexamethasone-induced muscle loss. Endocrinology 151, 1050–1059.CrossRefGoogle Scholar
Yang, Z. H., Miyahara, H., Mori, T., Doisaki, N. and Hatanaka, A. (2011). Beneficial effects of dietary fish-oil-derived monounsaturated fatty acids on metabolic syndrome risk factors and insulin resistance in mice. Journal of Agricultural and Food Chemistry 59, 7482–7489.CrossRefGoogle ScholarPubMed