Table 1.
Mouse cytokine and chemokine in DDR1 mice expressing LV α-synuclein and treated with BK40143 once daily for 3 weeks
| DDR1 knockout mice | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Genotype | WT | Het | KO | ||||||||
| Treatment | DMSO | 2.5 mg/kg BK40143 | WT drug P-value | DMSO | 2.5 mg/kg BK40143 | Het drug P-value | Het versus WT gene P-value | DMSO | 2.5 mg/kg BK40143 | KO drug P-value | KO versus WT gene P-value |
| n | 5 | 6 | 7 | 6 | 4 | 5 | |||||
| Marker (pg/ml) | Mean ± SD7 (% to DMSO) | Mean ± SD (% to DMSO) | Mean ± SD (% to DMSO) | Mean ± SD (% to DMSO) | Mean ± SD (% to DMSO) | Mean ± SD (% to DMSO) | |||||
| G-CSF | 3.43 ± 0.37 (100%) | 2.66 ± 0.904 (77%) | NS | 3.15 ± 2.06 (91%) | 3.25 ± 0.92 (94%) | NS | NS | 2.56 ± 0.72 (74% | 3.01 ± 1.19 (87%) | NS | NS |
| Eotaxin | 17.62 ± 1.69 (100%) | 18.48 ± 3.93 (104%) | NS | 19.95 ± 6.67 (113%) | 18.64 ± 1.59 (105%) | NS | NS | 16.72 ± 1.32 (94%) | 15.09 ± 2.12 (85%) | NS | NS |
| GM-CSF | 15.68 ± 4.28 (100%) | 12.61 ± 4.09 (80%) | NS | 14.85 ± 5.03 (94%) | 14.91 ± 4.77 (95%) | NS | NS | 12.95 ± 3.15 (82%) | 12 ± 4.30 (76%) | NS | NS |
| IFN-γ | 29.08 ± 7.60 (100%) | 26.99 ± 2.30 (92%) | NS | 26.91 ± 5.53 (92%) | 23.09 ± 1.51 (79%) | NS | NS | 22.03 ± 2.17 (75%) | 20.67 ± 4.13 (71%) | NS | NS |
| IL-1a | 153. 37 ± 24.96 (100%) | 143.32 ± 9.89 (93%) | NS | 147.68 ± 12.36 (96%) | 130.66 ± 6.42 (85%) | 0.011487 | NS | 138.39 ± 22.37 (90%) | 134.38 ± 13.74 (87%) | NS | NS |
| IL-1b | 8.45 ± 1.98 (100%) | 8.10 ± 1.57 (95%) | NS | 9.72 ± 1.57 (115%) | 9.03 ± 3.74 (106%) | NS | NS | 8.66 ± 5.19 (102%) | 8.21 ± 2.87 (97%) | NS | NS |
| IL-2 | 167.38 ± 53.77 (100%) | 170.06 ± 8.37 (101%) | NS | 161.95 ± 19.36 (96%) | 145.16 ± 10.92 (86%) | NS | NS | 154.05 ± 19.97 (92%) | 145.93 ± 11.87 (87%) | NS | NS |
| IL-3 | 0.84 ± 0.12 (100%) | 0.92 ± 0.14 (110%) | NS | 0.91 ± 0.15 (107%) | 0.85 ± 0.14 (101%) | NS | NS | 0.81 ± 0.09 (96%) | 0.75 ± 0.10 (89%) | NS | NS |
| IL-6 | 18 ± 15.99 (100%) | 15.87 ± 4.35 (88%) | NS | 12.2 ± 5.29 (67%) | 8.98 ± 1.28 (49%) | NS | NS | 9.26 ± 4.18 (51%) | 7.57 ± 3.18 (42%) | NS | NS |
| IL-7 | 5.41 ± 0.53 (100%) | 4.78 ± 0.62 (88%) | NS | 4.89 ± 0.28 (90%) | 5.59 ± 0.97 (103%) | NS | NS | 4.61 ± 0.38 (85%) | 4.38 ± 0.39 (80%) | NS | NS |
| IL-9 | 6491.8 ± 1095.36 (100%) | 5762.83 ± 1670.93 (88%) | NS | 5268.71 ± 1010.51 (81%) | 4965.33 ± 518.51 (76%) | NS | <0.0001 | 5667 ± 516.38 (87%) | 4957.8 ± 496.39 (76%) | NS | <0.0001 |
| IL-10 | 18.53 ± 2.58 (100%) | 20.17 ± 2.45 (108%) | NS | 19.77 ± 3.49 (106%) | 18.28 ± 0.53 (98%) | NS | NS | 17.3 ± 1.72 (93%) | 16.49 ± 2.50 (89%) | NS | NS |
| P-40 | 9.24 ± 0.63 (100%) | 9.15 ± 0.93 (98%) | NS | 9.16 ± 1.27 (99%) | 8.77 ± 1.83 (94%) | NS | NS | 7.58 ± 0.32 (82%) | 7.61 ± 2.1 (82%) | NS | NS |
| P-70 | 18.30 ± 2.72 (100%) | 19.15 ± 3.82 (104%) | NS | 17.90 ± 1.96 (97%) | 20.82 ± 4.66 (113%) | NS | NS | 16.9725 ± 4.89 (92%) | 15.35 ± 3.22 (83%) | NS | NS |
| LIF | 2.13 ± 0.25 (100%) | 1.84 ± 0.13 (86%) | 0.034751 | 2.18 ± 0.46 (102%) | 1.99 ± 0.45 (93%) | NS | NS | 1.76 ± 0.22 (82%) | 1.64 ± 0.23 (76%) | NS | NS |
| IL-13 | 217.11 ± 57 (100%) | 79.77 ± 86.38 (36%) | 0.01416 | 82.78 ± 56.03 (38%) | 52.49 ± 32. 42 (24%) | NS | NS | 109.06 ± 47.68 (50%) | 53.99 ± 27. 63 (24%) | NS | NS |
| IL-15 | 35.13 ± 3.12 (100%) | 35.79 ± 3.32 (101%) | NS | 37.51 ± 3.46 (106%) | 35.91 ± 7.20 (102%) | NS | NS | 34.12 ± 4.10 (97%) | 32.33 ± 5.31 (92%) | NS | NS |
| IL-17 | 56.18 ± 8.01 (100%) | 47.31 ± 10.06 (84%) | NS | 40.24 ± 3.68 (71%) | 36.79 ± 2.49 (65%) | NS | NS | 48.21 ± 7.90 (85%) | 41.35 ± 5.87 (73%) | NS | NS |
| IP-10 | 69. 13 ± 15.03 (100%) | 68.63 ± 11.67 (99%) | NS | 63.78 ± 4.16 (92%) | 59.09 ± 2.45 (85%) | 0.034207 | NS | 57.09 ± 2.19 (82%) | 51.68 ± 9.62 (74%) | NS | NS |
| KC | 74.37 ± 11.03 (100%) | 66.34 ± 16.94 (89%) | NS | 61.13 ± 8.62 (82%) | 52.91 ± 4.55 (71%) | NS | NS | 46.73 ± 5.12 (62%) | 43.41 ± 5.70 (58%) | NS | NS |
| MCP-1 | 286.04 ± 67.21 (100%) | 190.21 ± 78.05 (66%) | NS | 175.89 ± 77.85 (61%) | 138.33 ± 52.17 (48%) | NS | NS | 163.67 ± 28.54 (57%) | 134.02 ± 33.6 (46%) | NS | NS |
| MIP-1a | 1018.35 ± 148.98 (100%) | 909.49 ± 166.85 (89%) | NS | 809.13 ± 129.56 (79%) | 705.91 ± 36.49 (69%) | NS | NS | 845.9 ± 85.12 (83%) | 740.25 ± 82.92 (72%) | NS | NS |
| M-CSF | 20.1 ± 1.99 (100%) | 18.04 ± 2.15 (89%) | NS | 21.52 ± 3.44 (107%) | 21.17 ± 3.73 (105%) | NS | NS | 16.26 ± 1.17 (80%) | 15.62 ± 2.92 (77%) | NS | NS |
| MIP-2 | 82.82 ± 6.89 (100%) | 75.92 ± 11.88 (91%) | NS | 80.64 ± 13.74 (97%) | 84.81 ± 14.96 (102%) | NS | NS | 78.28 ± 4.19 (94%) | 76.04 ± 9.06 (91%) | NS | NS |
| MIG | 113.83 ± 13.24(100%) | 97.33 ± 19.39 (85%) | NS | 109.91 ± 36.15 (96%) | 98.055 ± 17.32 (86%) | NS | NS | 92.49 ± 9.59 (81%) | 90.42 ± 8.97 (70%) | NS | NS |
| VEGF | 6.94 ± 1.15 (100%) | 5.59 ± 1.43 (80%) | NS | 5.35 ± 0.82 (81%) | 4.83 ± 0.38 (78%) | NS | NS | 4.93 ± 0.44 (71%) | 4.414 ± 0.86 (67%) | NS | NS |
| TNF-α | 6.23 ± 1.15 (100%) | 4.99 ± 1.07 (80%) | NS | 5.06 ± 0.71 (81%) | 4.90 ± 0.99 (78%) | NS | NS | 4.47 ± 0.85 (71%) | 4.192 ± 0.66 (67%) | NS | NS |
BK40143 significantly reduces pro-inflammatory IL-1a in total brain lysates. IL-9 is significantly reduced in HET and KO mice compared with WT, suggesting that DDR1 deletion lowers IL-9 and the level of the pro-inflammatory downstream cytokine IP-10. GM-CSF: granulocyte–macrophage colony-stimulating factor, Eotaxin: CCL11 chemokine, P40: subunit, of IL-12 that drives polarization of Th17, a subset of T cell suspected to have a key role in the pathophysiology of MS and EAE, P70: IL-12p40 is thought to be a natural antagonist of IL-12p70, acting, at least in part, by competitive binding to the IL-12 receptor, LIF: leukemia inhibitory factor-interleukin 6 family cytokine that are pro-inflammatory, IP10: C-X-C motif chemokine 10 (CXCL10) also known as IFN-γ-IP that plays an pro-inflammatory role in autoimmune diseases, KC: pro-inflammatory chemokine (C-X-C motif) ligand 1 (CXCL1), MIP-1a cytokine also known as CCL3, MIP-2 is a major CXCL2 chemokine, M-CSF: macrophage colony-stimulating factor, MIG: monokine induced by γ-MIG), or CXCL9, is a chemokine induced by IFN-γ, RANTES: known as chemokine (C-C motif) ligand 5 (also CCL5) is a protein produced by T and B Lymphocytes, VEGF: vascular endothelial growth factor, TNF-α: tumor necrosis factor that is a cytokine mainly produced by macrophages. NS: not significant.