Ambrosius, Björn; Faissner, Simon; Guse, Kirsten; von Lehe, Marec; Grunwald, Thomas; Gold, Ralf; Grewe, Bastian; Chan, Andrew (2017). Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity. Journal of neuroinflammation, 14(1), p. 51. BioMed Central 10.1186/s12974-017-0829-2
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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: p < 0.001; IL-6: 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; p < 0.001) and monomethylfumarate treatment led to 2.9-fold lower CXCL10 secretion (p < 0.001). Reduced toxicity of co-culture conditioned media on human fetal neurons by teriflunomide (29%, p < 0.01) and monomethylfumarate (27%, p < 0.05) indicated functional relevance. Modulation of innate immune functions by teriflunomide and monomethylfumarate may target neurotoxic inflammation in the context of HAND.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Sahli Building > Forschungsgruppe Neurologie |
UniBE Contributor: |
Guse, Kirsten, Chan, Andrew Hao-Kuang |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1742-2094 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Stefanie Hetzenecker |
Date Deposited: |
21 Nov 2017 15:10 |
Last Modified: |
02 Mar 2023 23:29 |
Publisher DOI: |
10.1186/s12974-017-0829-2 |
PubMed ID: |
28284222 |
Uncontrolled Keywords: |
Dimethyl fumarate Glial activation HAND HIV-associated neurocognitive disorder Leflunomide Microglia Neuroinflammation |
BORIS DOI: |
10.7892/boris.106348 |
URI: |
https://boris.unibe.ch/id/eprint/106348 |
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