LEUKEMIA INHIBITORY FACTOR INDUCES THE 85-KDA CYTOSOLIC PHOSPHOLIPASEA(2) GENE-EXPRESSION IN CULTURED HUMAN BRONCHIAL EPITHELIAL-CELLS

Leukemia inhibitory factor (LIF) has become increasingly recognized as an important regulator of inflammation. This study is designed to det ermine whether LIF has an effect on arachidonate metabolism in human a irway epithelial cells. LIF (100 ng/ml) induced a significantly increa sed release of prelabeled [H-3] arachidonic acid (AA) from the human b ronchial epithelial cell line (BEAS 2B cell) as well as from the prima ry cultures of human bronchial epithelial cells. Exposure of the LIF s timulated BEAS 2B cells to calcium ionophore A23187 (10(-5) M, 15 min) caused a further increase of [3H]AA release. To identify the role of cytosolic phospholipase A(2) (cPLA(2)) in this upregulation of AA rele ase, further experiments were performed to determine the expression of cPLA(2) in the BEAS 2B cells. Immunoblot analysis indicated that LIF increased cPLA(2) protein expression. Ribonuclease protection assay sh owed that LIF induced an increase of cPLA(2) mRNA levels following 3 h to 24 h treatment. Nuclear run-on experiments suggested that LIF upre gulated cPLA, gene expression through post-translational regulation. T hese results demonstrate that LIF induces cPLA(2) gene expression and modulates arachidonate metabolism in airway epithelial cells.