Therapeutic effects of p38 mitogen-activated protein kinases inhibitor SB203580 on airway inflammation in a mouse model of asthma
Objective 
To investigate the effects of p38 mitogen-activated protein kinases (p38 MAPK) inhibitor (SB203580) on airway inflammation in a mouse model of asthma. 
 
 
Methods 
Forty-eight female BALB/c mice were randomly divided into four groups (n=12): control group, asthma group, dexamethasone group (2 mg/kg) and SB203580 group (5 mg/kg). Within 24 hours after the last ovalbumin (OVA) challenge, airway responsiveness was measured by lung resistance (RL) and dynamic compliance (Cdyn). Bronchoalveolar lavage fluid (BALF) was collected for counting total cells, eosinophils, lymphocytes, neutrophils and macrophages. IgE and OVA-specific IgE in serum and IL-4, IL-5, IL-13 and IFN-γ in BALF were detected by ELISA. Lung tissues were stained with hematoxylin and eosin (HE) and alcian blue-periodic acid-Schiff (AB-PAS) to observe histopathological changes. Expression of p38 MAPK and phosphorylated p38 (p-p38) MAPK was detected by immunohistochemical staining and Western blot, respectively. 
 
 
Results 
(1) The mice in the asthma group showed typical symptoms of acute asthma after inhaling aerosolized OVA, while the symptoms were alleviated in those treated with dexamethasone or SB203580. (2) When challenged with the methacholine at the doses of 0.050 mg/kg, 0.100 mg/kg and 0.200 mg/kg, asthmatic mice treated with dexamethasone or SB203580 showed significantly decreased RL and increased Cdyn as compared with those in the asthma group (all P 0.05). (8) Expression of p-p38 MAPK at protein level in both dexamethasone and SB203580 groups was lower than that in asthma group (both P<0.05). 
 
 
Conclusion 
SB203580 regulated the Th1/Th2 balance through inhibiting the activation of p38 MAPK signaling pathway to alleviate OVA-induced airway inflammation. 
 
 
Key words: 
Bronchial asthma; p38 mitogen-activated protein kinases; Cytokine; Airway inflammation; Mice