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Noor et al. Neuroimmunol Neuroinflammation 2019;6:10 I http://dx.doi.org/10.20517/2347-8659.2019.18 Page 21 of 32

A B

C D

E F

G H

Figure 7. Ipsilateral dorsal spinal cord mRNA levels reveal BIRT377 treatment reduces CCL2 in sciatic damaged females only, while no
sex differences occur in elevated IL-10. Lumbar spinal cord (LSC) tissues from behaviorally verified mice (Figure 2B), were collected and
analyzed for pain-relevant cytokines. (A-B) Ipsilateral CCL2 mRNA levels were increased following CCI (F 1,1 = 57.38, P < 0.0001). BIRT377
treatment reduced CCL2 mRNA expression in females with CCI (F 1,1 = 5.28, P = 0.026). Neuropathic females displayed significantly more
CCL2 mRNA levels than in neuropathic males (P = 0.006). Post hoc comparisons revealed significant reduction in contralateral CCL2
mRNA levels in CCI-treated females following BIRT377 treatment. (C-D) Ipsilateral IL-1β mRNA levels were increased following CCI (F 1,1
= 32.8, P < 0.0001) that occurred in females to much a greater degree than males (F 1,1 = 6.86, P = 0.012). (E-F) While sciatic nerve CCI
induced a bilateral elevation in TGF-β1 mRNA levels in both males and females (ipsilateral: F 1,1 = 40.95, P < 0.0001; contralateral: F 1,1 =
5.23, P = 0.027), the magnitude of TGF-β1 mRNA increase following BIRT377 treatment was greater in ipsilateral LSC from females than
males (F 1,1 = 6.56, P = 0.014). No differences in TGF-β1 mRNA levels from contralateral LSC were revealed following BIRT377 treatment.
(G-H) IL-10 mRNA levels were decreased following CCI (ipsilateral: F 1,1 = 52.26, P < 0.0001; contralateral: F 1,1 = 9.45, P = 0.004). BIRT377
treatment increased IL-10 mRNA expression levels in mice with CCI (ipsilateral: F 1,1 = 6.19, P = 0.017; contralateral: F 1,1 = 4.94, P = 0.032).
*P values from post hoc comparisons ranges from P = 0.04 to P < 0.0001. n = 5 in male Sham + Veh and CCI + BIRT for IL-10 contralateral
data. n = 6 per group unless otherwise indicated