Regulative effect of P38MAPK on release of TNF and NO from alveolar macrophages under endotoxin stimulation

Objective:: To evaluate activation of P38 mitogen-activated protein kinase (P38MAPK) in alveolar macrophage (AM), release of TNFα and NO from cells, and their relationship following lipopolysacchride (LPS) stimulation. Methods: AM was isolated from branch alveolar lavage fluid (BALF). The activation of P38MAPK was assayed by Westernblot. SB203580, a specific inhibitor of P38MAPK, was used with gradient concentration to evaluate the regulative effect of P38MAPK on the release of TNFα and NO from AM. Results: P38MAPK was activated by LPS (100 ng/ml ) with peak activation at 30 minutes. The activation of P38MAPK was inhibited by SB203580. The secretion of TNFα and NO stimulated with LPS increased (P 0.01 ) and was inhibited by SB203580 significantly. Conclusions: The results indicate that P38MAPK is involved in the secreting process of TNFα and NO following LPS stimulation. P38MAPK may be an important site for controlling the secretion of both inflammatory mediators during lung inflammatory disorders.