Therapeutic effects of p38 mitogen-activated protein kinases inhibitor SB203580 on airway inflammation in a mouse model of asthma / 中华微生物学和免疫学杂志

ABSTRACT

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). (3) The concentrations of total IgE and OVA-specific IgE in serum in both dexamethasone and SB203580 groups were lower than those in the asthma group (all P<0.05). (4) Compared with the asthma group, the numbers of the total cells, eosinophil, lymphocytes and neutrophils in BALF were decreased in dexamethasone and SB203580 groups (all P<0.05). (5) Compared with the asthma group, the dexamethasone and SB203580 groups showed lower levels of IL-4, IL-5 and IL-13, but higher levels of IFN-γ in BALF (all P<0.05). (6) Dexamethasone or SB203580 significantly decreased the hyperemia and edema in airway mucosa, reduced the infiltration of inflammatory cells in the peribronchial areas and alleviated the tracheal epithelium goblet cell metaplasia in asthmatic mice. (7) Treatment with dexamethasone or SB203580 inhibited OVA-induced phosphorylation of p38 MAPK in asthmatic mice as revealed by immunohistochemical staining (both P<0.05). No significant difference in the expression of p38 MAPK was observed among the four groups (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.