Inhibition of p38 mitogen-activated protein kinase augments lipopolysaccharide-induced cell proliferation in CD14-expressing Chinese hamster ovary cells

CD14-expressing Chinese hamster ovary (CD14-CHO) cells, established by tran sfection of human CD14 DNA, acquired high responsiveness to lipopolysacchar ide (LPS) through membrane-bound CD14 expression. LPS induced DNA synthesis and activated a series of mitogen-activated protein (MAP) kinases, extrace llular signal-regulated kinase 1/2 (Erk1/2), p38, and c-Jun N-terminal kina se/stress-activated protein kinase, in CD14-CHO cells but not in mock-trans fected CHO cells, Anti-CD14 antibody completely abrogated both LPS-induced DNA synthesis and LPS-induced phosphorylation of those MAP kinases, suggest ing a critical role of membrane-bound CD14 in LPS signaling. A p38 MAP kina se inhibitor, SB203580, markedly augmented LPS-induced DNA synthesis in CD1 4-CHO cells, whereas an Erk1/2 inhibitor, PD98059, had no affect. On the ot her hand, SB203580 exhibited no effect on epidermal growth factor-induced D NA synthesis in CD14-CHO cells, although PD98059 inhibited it significantly . The activation and inactivation of p38 IL MAP kinase with dominant negati ve and dominant positive mutants also suggested the participation of p38 MA P kinase in LPS-induced DNA synthesis. It was therefore suggested that the activation of p38 MAP kinase can negatively regulate LPS-induced cell proli feration in CD14-CHO cells.