Involvement of mitogen-activated protein kinase activation in cyclooxygenase-2 and transforming growth factor-β production in alveolar macrophage from chronic bronchitis rats

Abstract

Objective: Lipopolysaccharides (LPS) activates several signaling pathways in macrophages including mitogen-activated protein kinases (MAPK). Previous studies have investigated effect of LPS on MAPK activation in macrophage of normal rats. In the current study, we investigated the effect of LPS exposure on activation of MAPK in alveolar macrophage (AM) of chronic bronchitis (CB) rats and researched the corresponding cyclooxygenase-2 (COX-2), prostaglandins-2 (PGE2) and transforming growth factor- β (TGF-β) production and their MAPK signal pathways.Methods: CB model was established by injection of Bacillus Calmette-Guerin (BCG) and LPS in rats. Special inhibitors of p38, extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinases (JNK) MAPK signal pathways were used to determine the effect of MAPK activation on COX-2, PGE2, TGF-β production in AM of CB rats via RT-PCR, western blotting, radioimmunoassay and ELISA.Key findings: Synthesis of PGE2 from AM of CB rats was increased and suppressed by either PD98059 or SB203580. SB203580 and PD98059, (inhibitors of ERK and p38 MAPK), could significantly inhibit COX-2 mRNA and protein expression. Moreover, ERK and p38 MAPK had synergistic effect on COX-2 expression. Inhibitor of ERK MAPK signal transduction could inhibit TGF-β expression in AM.Conclusion: These results demonstrated COX-2, PGE2 and TGF-β productions in AM of CB rats were significantly increased, which might be regulated by the different MAPK signaling pathway.