Figure 5: Attenuation of cigarette smoke-induced neutrophilic airway inflammation by MS-275.

Experimental procedure (A). Male C57Bl/6 mice were exposed to cigarette smoke twice daily on four consecutive days by whole body exposure. Mice were subjected to MS-275 (10 μM by nebulization) or vehicle (inhibitor solvent) 30 min prior to each cigarette smoke exposure. Bronchoalveolar lavage (BAL) was performed and lungs were collected 16 h after the last smoke exposure. Gene expression in lung homogenates was studied by RT-qPCR and expressed relative to GAPDH (B). MS-275 robustly reduced IL1β and KC mRNA levels in cigarette smoke exposed mice. Data are presented as mean ± SD; n = 4–5 animals per group. **p < 0.01 compared to vehicle (smoke and inhibitor solvent-treated) group ^#p < 0.05 compared to air-exposed group. Release of KC in BAL fluid was determined by ELISA (C). MS-275 significantly reduced KC release in BAL fluid of cigarette-smoke exposed mice. Data are presented as mean ± SD; n = 4–5 animals per group. *p < 0.05 compared to vehicle (smoke and inhibitor solvent-treated) mice. Inflammatory cell count was performed in BAL fluid (D) and total cells, macrophages, lymphocytes and neutrophils were plotted as number of cells/ml (E). Total cell number in cigarette smoke exposed mice was not affected by MS-275. Neutrophilic infiltration was reduced by 60% in MS-275-treated mice compare to vehicle (smoke and inhibitor solvent-treated) mice. Data are presented as mean ± SD; n = 4–5 animals per group. *p < 0.05 compared to vehicle (smoke and inhibitor solvent-treated) mice.