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Journal of Clinical Immunology

Erschienen in:

01.12.2011

Immunosuppressive Effects and Mechanisms of Leflunomide in Dengue Virus Infection of Human Dendritic Cells

verfasst von: Wan-Lin Wu, Ling-Jun Ho, Pei-Chih Chen, Yi-Ting Tsai, Seng-Ting Hsu, Deh-Ming Chang, Jenn-Haung Lai

Erschienen in: Journal of Clinical Immunology | Ausgabe 6/2011

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Abstract

Background

Dengue virus (DENV) infection is a serious public health issue without specific treatment. We examined the potential immunomodulatory effects of leflunomide, a dihydroorotate dehydrogenase inhibitor commonly prescribed for arthritis, in DENV-stimulated monocyte-derived dendritic cells (mo-DCs).

Methods

mo-DCs were prepared from purified monocytes. Cytokine and chemokine concentrations were determined by enzyme-linked immunosorbent assay. Expression of cell surface markers or viral E protein was measured by flow cytometry. The activation of transcription factors and kinases was determined by electrophoretic mobility shift assays, Western blotting, or immunoprecipitation kinase assays. Chemotaxis assays were used to determine cell migration.

Results

Leflunomide at therapeutic concentrations inhibited cytokine and chemokine production from DENV-infected mo-DCs. Leflunomide suppressed mo-DC maturation by downregulating the expression of both CD80 and CD86. In addition, leflunomide inhibited DENV-induced mo-DC migration and mo-DC response to chemoattractants CCL19 and CCL21. Inhibition of mo-DC migration was likely due to the suppression of CCR7 expression on mo-DCs. These events were associated with the suppression of nuclear factor kappa B and activator protein-1 signaling pathways by leflunomide.

Conclusions

Leflunomide preserves immunosuppressive effects, inhibiting activation of DENV-stimulated mo-DCs. Leflunomide may be helpful in the development of therapeutics for DENV infection.

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Titel: Immunosuppressive Effects and Mechanisms of Leflunomide in Dengue Virus Infection of Human Dendritic Cells
verfasst von: Wan-Lin Wu
Ling-Jun Ho
Pei-Chih Chen
Yi-Ting Tsai
Seng-Ting Hsu
Deh-Ming Chang
Jenn-Haung Lai
Publikationsdatum: 01.12.2011
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 6/2011
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-011-9578-7

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Immunosuppressive Effects and Mechanisms of Leflunomide in Dengue Virus Infection of Human Dendritic Cells

Abstract

Background

Methods

Results

Conclusions

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