Table 2.
Dose-dependent annotated activities on clinically relevant biomarkers of: C15:0 (FA15) (1.9, 5.6, 17, 50 µM), rapamycin (0.3, 1, 3, 9 µM), metformin (190, 560, 1700, 5000 µM), and acarbose (1.1, 3.3, 10, 30 µM) among 12 primary human cell systems mimicking various disease states. Eicosapentaenoic acid (EPA), previously published, is included as a reference [25]. Based on the accepted BioMAP procedures, biomarker activities were annotated when 2 or more consecutive concentrations changed in the same direction relative to vehicle controls, were outside of the significance envelope, and had at least one concentration with an effect size >20% (|log10 ratio| > 0.1). Up arrows indicate that the measured biomarker was significantly higher than the significance envelope (higher than non-treated vehicle controls); down arrows indicate that the measured biomarker was significantly lower than the significance envelope (lower than non-treated vehicle controls).
| BioMAP Phenotypic Cell Profiles | Dose-Dependent Annotated Activities by Compounds on Clinically Relevant Biomarkers |
||||||
|---|---|---|---|---|---|---|---|
| BioMAP Cell System | Human Cell Types and Stimulation | Disease Relevance | C15:0 (FA15TM) (1.9–50 µM) |
Rapamycin (0.3–9 µM) |
Metformin (190–5000 µM) |
Acarbose (1.1–30 µM) |
Omega-3 (EPA) [25] (1.9–17 µM) |
| 3C | Venular endothelial cells stimulated with TNFα, IL-1β, IFNγ | Cardiovascular disease, chronic inflammation | ↓ HLA-DR ↓ MCP-1 ↓ proliferation |
↓ HLA-DR ↓ VCAM-1 ↓ uPAR ↓ proliferation |
↓ HLA-DR ↓ IL-8 |
None | ↓ MCP-1 ↓ uPAR |
| 4H | Venular endothelial cells stimulated with IL-4, histamine | Autoimmunity, allergy, asthma | ↓ Eot3 | ↓ MCP-1 | None | None | None |
| LPS | Venular endothelial cells and peripheral blood mononuclear cells stimulated with TLR4 ligand | Chronic inflammation, cardiovascular disease | ↓ VEGFR2 ↓ MCP-1 ↓ CD69 ↓ IL-1α |
↓ CD40 | ↓ CD40 | None | None |
| SAg | Venular endothelial cells and peripheral blood mononuclear cells stimulated with TCR ligands | Chronic inflammation, autoimmune disease | ↓ CD38 ↓ CD40 ↓ CD69 ↓ T cell proliferation |
↓ CD38 ↓ CD40 ↓ MCP-1 ↓ T cell proliferation |
↓ CD38 ↓ CD69 ↓ T cell proliferation |
None | None |
| BT | Peripheral blood mononuclear cells and B cells stimulated with αIgM, TCR ligands | Asthma, cancer, autoimmunity, allergy | ↓ IgG ↓ IL-17F |
↓ IgG ↓ IL-17F ↓ TNFα ↓ IL-6 ↓ IL-2 ↓ IL-17A ↓ proliferation |
None | None | None |
| BF4T | Bronchial epithelial cells and dermal fibroblasts stimulated with IL-4, TNFα | Fibrosis, lung inflammation, asthma, allergy | None | ↓ VCAM-1 ↓ tPA |
↓ MCP-1 ↓ tPA |
None | ↓ PAI-I |
| BE3C | Bronchial epithelial cells stimulated with IL-1β, IFNγ, TNFα | COPD, lung inflammation | ↓ tPA | ↓ tPA | ↓ IP-10 ↓ IL-8 ↓ HLA-DR ↓ MMP9 |
None | None |
| CASM3C | Coronary artery smooth muscle cells stimulated with IL-1β, TNFα, IFNγ | Cardiovascular inflammation, restenosis | ↓ HLA-DR ↓ IL-6 ↓ VCAM-1 ↓ TM ↓ TF ↓ proliferation |
↓ HLA-DR ↓ uPAR ↓ proliferation |
None | ↓ uPAR | None |
| HDF3CGF | Dermal fibroblasts stimulated with IFNγ, TNFα, IL-1β, EGT, bFGF, PDGF-BB | Fibrosis, chronic inflammation | ↓ PAI-1 ↓ VCAM-1 ↓ IP-10 ↓ ITAC ↓ MIG ↓ fibroblast proliferation |
↓ PAI-I ↓ EGFR ↓ fibroblast proliferation |
↓ Col-III | ↓ EGFR ↓ fibroblast proliferation |
↓ PAI-I ↓ M-CSF |
| KF3CT | Keratinocytes, dermal fibroblasts stimulated with IL-1β, IFNγ, TGFβ, TNFα | Dermatitis, psoriasis | None | ↓ PAI-I | None | None | None |
| MyoF | Lung fibroblasts stimulated with TGFβ, TNFα | Wound healing, matrix remodeling, fibrosis, chronic inflammation | ↓ VCAM-1 ↓ Col-I ↓ IL-8 ↓ Decorin ↓ TIMP-1 |
↓ VCAM-1 ↓ PAI-I |
None | ↓ Col-IV ↓TIMP1 |
↓ Col-I ↓ Col-III |
| /Mphg | Macrophages and venular endothelial cells stimulated with TLR2 ligand | Chronic inflammation, restenosis, cardiovascular disease | ↓ CD40 ↓ CD69 |
↓ sIL-10 | ↓ MCP-1 ↓ Esel ↓ IL-8 |
None | None |