fig3

Figure 3. BIRT377 treatment reduced pro-inflammatory cytokine/chemokine in males and females and increased anti-inflammatory cytokines only in females around the injured sciatic nerve. Ipsilateral sciatic nerves were collected from behaviorally verified mice as represented in Figure 2B. (A) Sciatic nerve damage (CCI) induced a significant increase in CCL2 mRNA expression (F_1,1 = 16.33, P = 0.0002), which was greater males than females (F_1,1 = 4.36, P = 0.043). BIRT377 treatment reduced CCL2 mRNA expression in male mice with CCI (F_1,1 = 7.43, P = 0.009). (B) CCI increased IL-1β mRNA expression (F_1,1 = 54.46, P < 0.0001), which was greater in males than females (F_1,1 = 9.68, P = 0.003). BIRT377 treatment reduced IL-1β mRNA levels in mice with CCI (F_1,1 = 16.3, P = 0.0002). (C) Similarly, after CCI, TNF mRNA expression was elevated (F_1,1 = 35.85, P < 0.0001). BIRT377 treatment reduced TNF mRNA expression in mice with CCI (F_1,1 = 11.53, P = 0.001). (D) Following CCI, IL-10 mRNA was dramatically increased (F_1,1 = 83.79, P < 0.0001). BIRT377 treatment further induced IL-10 mRNA expression in females, as a significant interaction between BIRT377 treatment and sex (F_1,1 = 4.35, P = 0.04) was observed. (E) CCI induced an increase in TGF-β1 mRNA expression (F_1,1 = 52.7, P < 0.0001). BIRT377 treatment further increased TGF-β1 in female s with CCI (F_1,1 = 6.98, P = 0.012). (F) After CCI, CD11b mRNA levels were increased (F_1,1 = 104.2, P < 0.0001). Following CCI, males displayed greater levels of CD11b mRNA than females (F_1,1 = 4.58, P = 0.038). BIRT377 treatment reduced CD11b mRNA levels in male mice with CCI (F_1,1 = 4.884, P = 0.032) but not females, as a main effect of sex was observed for CD11b mRNA levels (F_1,1 = 4.22, P = 0.046). (G) CD3 mRNA levels were elevated in mice with CCI (F_1,1 = 34.3, P < 0.0001). Post hoc comparisons revealed that BIRT377 treatment reduced CD3 levels in males with CCI (P = 0.016). *p values from post hoc comparisons ranges from P = 0.039 to P < 0.0001. n = 5 in female Sham + Veh and CCI + Veh for TGF-β1 data. n = 6 per group unless otherwise indicated