Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity
- HIV-associated neurocognitive disorders (HAND) affect about 50% of infected patients despite combined antiretroviral therapy (cART). Ongoing compartmentalized inflammation mediated by microglia which are activated by HIV-infected monocytes has been postulated to contribute to neurotoxicity independent from viral replication. Here, we investigated effects of teriflunomide and monomethylfumarate on monocyte/microglial activation and neurotoxicity. Human monocytoid cells (U937) transduced with a minimal HIV-Vector were co-cultured with human microglial cells (HMC3). Secretion of pro-inflammatory/neurotoxic cytokines (CXCL10, CCL5, and CCL2: \(\it p\)< 0.001; IL-6: \(\it p\)< 0.01) by co-cultures was strongly increased compared to microglia in contact with HIV-particles alone. Upon treatment with teriflunomide, cytokine secretion was decreased (CXCL10, 3-fold; CCL2, 2.5-fold; IL-6, 2.2-fold; \(\it p\)<0.001) and monomethylfumarate treatment led to 2.9-fold lower CXCL10 secretion (\(\it p\)< 0.001). Reduced toxicity of co-culture conditioned media on human fetal neurons by teriflunomide (29%, \(\it p\)< 0.01) and monomethylfumarate (27%, \(\it p\)< 0.05) indicated functional relevance. Modulation of innate immune functions by teriflunomide and monomethylfumarate may target neurotoxic inflammation in the context of HAND.
Author: | Björn AmbrosiusGND, Simon Raoul FaissnerORCiDGND, Kirsten GuseGND, Marec von LeheGND, Thomas GrunwaldORCiDGND, Ralf GoldORCiDGND, Bastian GreweGND, Andrew ChanGND |
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URN: | urn:nbn:de:hbz:294-58810 |
DOI: | https://doi.org/10.1186/s12974-017-0829-2 |
Parent Title (English): | Journal of neuroinflammation |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2018/07/10 |
Date of first Publication: | 2017/03/11 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds Dimethyl fumarate; Glial activation; HAND; HIV-associated neurocognitive disorder; Leflunomide; Microglia; Neuroinflammation |
Volume: | 14 |
Issue: | 1 |
First Page: | 51-1 |
Last Page: | 51-10 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | St. Josef-Hospital Bochum, Neurologische Klinik |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
faculties: | Medizinische Fakultät |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |