Table 1.
Effects of dimethyl fumarate (DMF) and monomethyl fumarate (MMF) on different cell lineages relevant to HIV infection.
| Cell Type | DMF/MMF | Cytokine/Receptor Expression changes |
Effects | References |
|---|---|---|---|---|
| T-cells | DMF | ↑ IL-4, IL-10 ↔ CCR4, IL-5 ↓ NF-κB DNA binding, INFγ, CXCR3 CXCR10, IL-6, TGFα, CD25, CLA | TH1 → Th2 shift ↓ endothelial rolling, firm adhesion, & tissue infiltration ↓ binding to E-selectin, P-selectin, and VCAM-1 | 47–51, 53 |
| MMF | ↑ IL-4, IL-5 ↔ NF-κB DNA binding, INFγ, IL-2 | Th1 → Th2 shift ↓ dendritic cell differentiation | ||
| PBMCs | DMF | ↓ CXCL8,CXCL9, CXCL10 | Th1 → Th2 shift ↓ macrophage inflammatory cytokine production ↓ leukocyte rolling | 47, 52, 53 |
| MMF | ↑ IL-4, IL-10, IL-5 ↔ INFγ, IL12, IL-2 | Th1 → Th2 shift | ||
| Monocyte/Macrophages | DMF | ↑ Nrf2 ↓ NF-κB nuclear translocation & DNA binding, TNFα, CCR2 | ↑ Antioxidant response, ↑ HO-1 ↑ superoxide anion ↓ CCL2-induced chemotaxis | 54, 57 |
| MMF | ↑ Nrf2 ↓ NF-κB nuclear translocation | ↑ Antioxidant response, ↑ HO-1 ↑ superoxide anion ↓ CCL2-induced chemotaxis | ||
| Dendritic Cells | DMF | ↑ IL-10 ↓ NF-κB activity (less free p65), IL-12, IL-6, IL-23 | ↑ Type II dendritic cells ↓Monocyte dendritic cell differentiation ↓ intracellular glutathione levels | 59–63 |
| MMF | ↓ NF-κB activity (less free p65), IL-12, IL-10, TNFα, IFNγ | ↑ Type II dendritic cells ↓Monocyte dendritic cell differentiation ↓ effectiveness in stimulating Th1 cytokine production in T cells | ||
| Endothelial cells | DMF | ↔NF-κB DNA binding ↓NF-κB nuclear entry, E-selectin, VCAM-1, ICAM-1 | ↓ TNFα indicated cytokine release ↓ leukocyte rolling and firm adhesion | 64–67 |
| MMF | ↔ NF-κB DNA binding, E-selectin, VCAM-1, ICAM-1 | ? | ||
| Microglia | DMF | ↑ Nrf2 expression ↓ IL-1β, IL-6, TNFα, iNOS | ↑ Antioxidiant response, ↑ HO-1 ↓ Nitrites | 55,56 |
| MMF | ↑ Nrf2 | ↑ Antioxidant response, ↑ HO-1 | ||
| Astrocytes | DMF | ↑Nrf2 expression, nuclear entry, and DNA binding ↓ IL-1β, IL-6, TNFα | ↑ Antioxidant response, ↑ HO-1 ↑ Viability after oxidative stress | 55, 69, 70 |
| MMF | ↑Nrf2 expression, nuclear entry, and DNA binding | ↑ Antioxidant response, ↑ HO-1 ↑ viability after oxidative stress (Nrf2-depdent) | ||
| Neurons | DMF | ↑Nrf2 nuclear entry ↔ NF-κB nuclear entry | ↑ Antioxidant response ↑ viability post oxidative & glutamate toxicity (Nrf2-dependent) | 69–71 |
| MMF | ↑Nrf2 nuclear entry | ↑ Antioxidant response ↑ viability post oxidative stress (Nrf2-dependent) ↔ viability post glutamate toxicity |