RETINOIC ACID POTENTLY STIMULATES THE PRODUCTION OF GRANULOCYTE-COLONY-STIMULATING FACTOR IN THE HUMAN MONOCYTIC THP-1 CELL-LINE

Lipopolysaccharide (LPS) potently induces the production of several cy tokines in THP-1 cells pretreated with phorbol 12-myristate 13-acetate (PMA). We report that all-trans retinoic acid (tRA) synergizes with L PS to enhance the production of granulocyte colony-stimulating factor (G-CSF) in PMA-treated cells, whereas the production of granulocyte-ma crophage CSF, interleukin 1-beta (IL-1-beta), and tumor necrosis facto r-alpha (TNF-alpha) is minimally affected by tRA. The interaction betw een LPS and tRA on G-CSF production is not due to IL-1-beta or TNF-alp ha present in the culture medium during LPS and tRA treatment because neutralization of n-1-beta and TNF-alpha activity does not inhibit the synergy between LPS and tRA. However, exogenous IL-1-beta, but not TN F-alpha, also synergizes with tRA on G-CSF production, suggesting that LPS and IL-l-beta can independently interact with tRA to stimulate G- CSF production.