Fig. 2.

ARA290 mitigates the inflammatory response in burn wounds. (A) Leukocyte infiltration of burn wounds with leukocytes generally correlates with RVA (n ≥ 3, mean ± SD, *P < 0.05 vs. control untreated burn wounds). (B) ARA290 alters the spatiotemporal dynamics of MPO activity within the wound. In central areas, MPO activity remains elevated in ARA290-treated wounds but drops ∼10 fold within 16 h in controls. At the wound edge, MPO activity is slightly above initial and decreases at 48 h in controls, whereas it increases steadily over time in ARA290-treated wounds (animals/time point = 3–8). ARA290 or vehicle was given at times denoted by arrows along the horizontal axis. (C and D) In contrast, ARA290-dependent suppression of TNF-α secretion is evident in nonnecrotic wound areas that are infiltrated by leukocytes. (E) Results of inflammatory response profiling based on the qPCR/ΔΔCt-method show that TNF-α, FAS, and IκBα, but not NF-κB, are up-regulated in control wounds harvested 24 h postburn. This response is largely suppressed by ARA290 treatment. (F) Expression of adhesion molecules PECAM-1 and VCAM-1 was increased in control wounds harvested 24 h postburn vs. normal healthy skin. ARA290 suppressed PECAM-1 and to a lesser extent VCAM-1 induction. (D and E) Samples (n = 3, mean± SD) were normalized against normal, healthy skin; *P < 0.05 vs. control untreated burn wounds.